40 results on '"Streicher, Katie"'
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2. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Arbetter, Douglas, Seegobin, Seth, Kiazand, Alexandre, Streicher, Katie, Martinez-Alier, Nuria, Cohen, Taylor S., and Esser, Mark T.
- Published
- 2024
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3. Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Patients with Moderate to Severe Asthma: The Phase 3b VECTOR Study
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Cole, Jeremy, Cąpała-Szczurko, Iwona, Roseti, Stephanie, Chen, Claudia, Caveney, Scott, Aksyuk, Anastasia A., Streicher, Katie, Ponnarambil, Sandhia, and Colice, Gene
- Published
- 2024
- Full Text
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4. Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial)
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Kijak, Gustavo H., Ahani, Bahar, Arbetter, Douglas, Chuecos, Fernando, Gopalakrishnan, Vancheswaran, Beloor, Jagadish, Brady, Tyler, Nguyen, Amy, Roe, Tiffany L., Schuko, Nicolette, Zhang, Tianhui, Hobbs, F. D. Richard, Padilla, Francisco, Kelly, Elizabeth J., Montgomery, Hugh, and Streicher, Katie
- Published
- 2023
- Full Text
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5. Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Kim, Kenneth, Arbetter, Douglas, Padilla, Kelly W., Reddy, Venkatesh Pilla, Seegobin, Seth, Streicher, Katie, Templeton, Alison, Viani, Rolando M., Johnsson, Eva, Koh, Gavin C. K. W., and Esser, Mark T.
- Published
- 2023
- Full Text
- View/download PDF
6. Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study
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Sahner, David, Tierney, John, Vogel, Susan E., Herpin, Betsey R., Smolskis, Mary C., McKay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Raim, Sharon Segal, Hensely, Lisa, Lorenzo, Johsua, Mock, Rebecca, Zuckerman, Judith, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Kang, Nayon, Barrett, Kevin, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Currier, Judy, Hughes, Eric, Harrigan, Rachel H., Amos, Laura, Carlsen, Amy, Carter, Anita, Collins, Gary, Davis, Bionca, Denning, Eileen, DuChene, Alain, Eckroth, Kate, Engen, Nicole, Frase, Alex, Gandits, Greg, Grund, Birgit, Harrison, Merrie, Hurlbut, Nancy, Kaiser, Payton, Koopmeiners, Joseph, Larson, Gregg, Meger, Sue, Mistry, Shweta Sharma, Murray, Thomas, Nelson, Ray, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Siegel, Lianne, Thompson, Greg, Vock, David, Walski, Jamie, Gelijns, Annetine C., Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Burris, Sarah, Bedoya, Gabriela, Gupta, Lola, Overbey, Jessica R., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Sandkovsky, Uriel, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samatha, Wang, Samatha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacious, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Smith, Peter K., Barkauskas, Christina E., Vekstein, Andrew M., Ko, Emily R., Dreyer, Grace R., Stafford, Neil, Brooks, Megan, Der, Tatyana, Witte, Marie, Gamarallage, Ruwan, Franzone, John, Ivey, Noel, Lumsden, Rebecca H., Mosaly, Nilima, Mourad, Ahmaad, Holland, Thomas L., Motta, Mary, Lane, Kathleen, McGowan, Lauren M., Stout, Jennifer, Aloor, Heather, Bragg, Kennesha M., Toledo, Barvina, McLendon-Arvik, Beth, Bussadori, Barbara, Hollister, Beth A., Griffin, Michelle, Giangiacomo, Dana M., Rodriguez, Vicente, Bokhart, Gordon, Eichman, Sharon M., Parrino, Patrick E., Spindel, Stephen, Bansal, Aditya, Baumgarten, Katherine, Hand, Johnathan, Vonderhaar, Derek, Nossaman, Bobby, Sylvia Laudun, Ames, DeAnna, Broussard, Shane, Hernandez, Nilmo, Isaac, Geralyn, Dinh, Huan, Zheng, Yiling, Tran, Sonny, McDaniel, Hunter, Crovetto, Nicolle, Perin, Emerson, Costello, Briana, Manian, Prasad, Sohail, M. Rizwan, Postalian, Alexander, Hinsu, Punit, Watson, Carolyn, Chen, James, Fink, Melyssa, Sturgis, Lydia, Walker, Kim, Mahon, Kim, Parenti, Jennifer, Kappenman, Casey, Knight, Aryn, Sturek, Jeffrey M., Barros, Andrew, Enfield, Kyle B., Kadl, Alexandra, Green, China J., Simon, Rachel M., Fox, Ashley, Thornton, Kara, Adams, Amy, Badhwar, Vinay, Sharma, Sunil, Peppers, Briana, McCarthy, Paul, Krupica, Troy, Sarwari, Arif, Reece, Rebecca, Fornaresico, Lisa, Glaze, Chad, Evans, Raquel, Di, Fang, Carlson, Shawn, Aucremanne, Tanja, Tennant, Connie, Sutton, Lisa Giblin, Buterbaugh, Sabrina, Williams, Roger, Bunner, Robin, Traverse, Jay H., Rhame, Frank, Huelster, Joshua, Kethireddy, Rajesh, Davies, Irena, Salamanca, Julianne, Majeski, Christine, Skelton, Paige, Zarambo, Maria, Sarafolean, Andrea, Bowdish, Michael E., Borok, Zea, Wald-Dickler, Noah, Hutcheon, Douglass, Towfighi, Amytis, Lee, Mary, Lewis, Meghan R., Spellberg, Brad, Sher, Linda, Sharma, Aniket, Olds, Anna P., Justino, Chris, Loxano, Edward, Romero, Chris, Leong, Janet, Rodina, Valentina, Quesada, Christine, Hamilton, Luke, Escobar, Jose, Leshnower, Brad, Bender, William, Sharifpour, Milad, Miller, Jeffrey, Farrington, Woodrow, Baio, Kim T., McBride, Mary, Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Maton, Missy, Ponder, Chari, Haley, Elisabeth, Spainhour, Christine, Rogers, Susan, Tyler, Derrick, Madathil, Ronson J., Rabin, Joseph, Levine, Andrea, Saharia, Kapil, Tabatabai, Ali, Lau, Christine, Gammie, James S., Peguero, Maya-Loren, McKernan, Kimberly, Audette, Mathew, Fleischmann, Emily, Akbari, Kreshta, Lee, Myounghee, Chi, Andrew, Salehi, Hanna, Pariser, Alan, Nyguyen, Phuong Tran, Moore, Jessica, Gee, Adrienne, Vincent, Shelika, Zuckerman, Richard A., Iribarne, Alexander, Metzler, Sara, Shipman, Samantha, Johnson, Haley, Newton, Crystallee, Parr, Doug, Miller, Leslie, Schelle, Beth, McLean, Sherry, Rothbaum, Howard R., Alvarez, Michael S., Kalan, Shivam P., Germann, Heather H., Hendershot, Jennifer, Moroney, Karen, Herring, Karen, Cook, Sharri, Paul, Pam, Walker-Ignasiak, Rebecca, North, Crystal, Oldmixon, Cathryn, Ringwood, Nancy, Muzikansky, Ariela, Morse, Richard, Fitzgerald, Laura, Morin, Haley D., Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Steingrub, Jay H., Hou, Peter K., Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, DeSouza, Leslie, Romain, Sarah, Thornton-Thompson, Sherell, Talmor, Daniel, Shapiro, Nathan, Andromidas, Konstantinos, Banner-Goodspeed, Valerie, Bolstad, Michael, Boyle, Katherine L., Cabrera, Payton, deVilla, Arnaldo, Ellis, Joshua C., Grafals, Ana, Hayes, Sharon, Higgins, Conor, Kurt, Lisa, Kurtzman, Nicholas, Redman, Kimberly, Rosseto, Elinita, Scaffidi, Douglas, Filbin, Michael R., Hibbert, Kathryn A., Parry, Blair, Margolin, Justin, Hillis, Brooklynn, Hamer, Rhonda, Brait, Kelsey, Beakes, Caroline, McKaig, Brenna, Kugener, Eleonore, Jones, Alan E., Galbraith, James, Nandi, Utsav, Peacock, Rebekah, Hendey, Gregory, Kangelaris, Kirsten, Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Yee, Kimberley J., Jauregui, Alejandra E., Zhuo, Hanjing, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley A., Hughes, Alyssa R., Garcia, Rebekah L., Lim, George W., Chang, Steven Y., Lin, Michael Y., Vargas, Julia, Sihota, Hena, Beutler, Rebecca, Agarwal, Trisha, Wilson, Jennifer G., Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan H., Roque, Jonasel, Wang, Henry, Huebinger, Ryan M., Patel, Bela, Vidales, Elizabeth, Albertson, Timothy, Hardy, Erin, Harper, Richart, Moss, Marc A., Baduashvili, Amiran, Chauhan, Lakshmi, Douin, David J., Martinez, Flora, Finck, Lani L., Bastman, Jill, Howell, Michelle, Higgins, Carrie, McKeehan, Jeffrey, Finigan, Jay, Stubenrauch, Peter, Janssen, William J., Griesmer, Christine, VerBurg, Olivia, Hyzy, Robert C., Park, Pauline K., Nelson, Kristine, McSparron, Jake I., Co, Ivan N., Wang, Bonnie R., Jimenez, Jose, Olbrich, Norman, McDonough, Kelli, Jia, Shijing, Hanna, Sinan, Gong, Michelle N., Richardson, Lynne D., Nair, Rahul, Lopez, Brenda, Amosu, Omowunmi, Offor, Obiageli, Tzehaie, Hiwet, Nkemdirim, William, Boujid, Sabah, Mosier, Jarrod M., Hypes, Cameron, Campbell, Elizabeth Salvagio, Bixby, Billie, Gilson, Boris, Lopez, Anitza, Bime, Christian, Parthasarathy, Sairam, Cano, Ariana M., Hite, R. Duncan, Terndrup, Thomas E., Wiedemann, Herbert P., Hudock, Kristin, Tanzeem, Hammad, More, Harshada, Martinkovic, Jamie, Sellers, Susan, Houston, Judy, Burns, Mary, Kiran, Simra, Roads, Tammy, Kennedy, Sarah, Duggal, Abhijit, Thiruchelvam, Nirosshan, Ashok, Kiran, King, Alexander H., Mehkri, Omar, Dugar, Siddharth, Sahoo, Debasis, Yealy, Donald M., Angus, Derek C., Weissman, Alexandra J., Vita, Tina M., Berryman, Emily, Hough, Catherine L., Khan, Akram, Krol, Olivia F., Mills, Emmanuel, Kinjal, Mistry, Briceno, Genesis, Reddy, Raju, Hubel, Kinsley, Jouzestani, Milad K., McDougal, Madeline, Deshmukh, Rupali, Johnston, Nicholas J., Robinson, Bryce H., Gundel, Staphanie J., Katsandres, Sarah C., Chen, Peter, Torbati, Sam S., Parimon, Tanyalak, Caudill, Antonina, Mattison, Brittany, Jackman, Susan E., Chen, Po-En, Bayoumi, Emad, Ojukwu, Cristabelle, Fine, Devin, Weissberg, Gwendolyn, Isip, Katherine, Choi-Kuaea, Yunhee, Mehdikhani, Shaunt, Dar, Tahir B., Fleury Augustin, Nsole Biteghe, Tran, Dana, Dukov, Jennifer Emilow, Matusov, Yuri, Choe, June, Hindoyan, Niree A., Wynter, Timothy, Pascual, Ethan, Clapham, Gregg J., Herrera, Lisa, Caudill, Antonia, O’Mahony, D. Shane, Nyatsatsang, Sonam T., Wilson, David M., Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Miller, Chadwick, Files, D. Clark, Gibbs, Kevin W., Flores, Lori S., LaRose, Mary E., Landreth, Leigha D., Palacios, D. Rafael, Parks, Lisa, Hicks, Madeline, Goodwin, Andrew J., Kilb, Edward F., Lematty, Caitlan T., Patti, Kerilyn, Grady, Abigail, Rasberry, April, Morris, Peter E., Sturgill, Jamie L., Cassity, Evan P., Dhar, Sanjay, Montgomery-Yates, Ashley A., Pasha, Sarah N., Mayer, Kirby P., Pharm.D., Brittany Bissel, Trott, Terren, Rehman, Shahnaz, de Wit, Marjolein, Mason, Jessica, Bledsoe, Joseph, Knowlton, Kirk U., Brown, Samuel, Lanspa, Michael, Leither, Lindsey, Pelton, Ithan, Armbruster, Brent P., Montgomery, Quinn, Kumar, Naresh, Fergus, Melissa, Imel, Karah, Palmer, Ghazal, Webb, Brandon, Klippel, Carolyn, Jensen, Hannah, Duckworth, Sarah, Gray, Andrew, Burke, Tyler, Knox, Dan, Lumpkin, Jenna, Aston, Valerie T., Applegate, Darrin, Serezlic, Erna, Brown, Katie, Merril, Mardee, Harris, Estelle S., Middleton, Elizabeth A., Barrios, Macy A.G., Greer, Jorden, Schmidt, Amber D., Webb, Melissa K., Paine, Roert, Callahan, Sean J., Waddoups, Lindsey J., Yamane, Misty B., Self, Wesley H., Rice, Todd W., Casey, Jonathan D., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Menon, Vidya, Kasubhai, Moiz, Pillai, Anjana, Daniel, Jean, Sittler, Daniel, Kanna, Balavenkatesh, Jilani, Nargis, Amaro, Francisco, Santana, Jessica, Lyakovestsky, Aleksandr, Madhoun, Issa, Desroches, Louis Marie, Amadon, Nicole, Bahr, Alaa, Ezzat, Imaan, Guerrero, Maryanne, Padilla, Joane, Fullmer, Jessie, Singh, Inderpreet, Ali Shah, Syed Hamad, Narang, Rajeev, Mock, Polly, Shadle, Melissa, Hernandez, Brenda, Welch, Kevin, Payne, Andrea, Ertl, Gabriela, Canario, Daniel, Barrientos, Isabel, Goss, Danielle, DeVries, Mattie, Folowosele, Ibidolapo, Garner, Dorothy, Gomez, Mariana, Price, Justin, Bansal, Ekta, Wong, Jim, Faulhaber, Jason, Fazili, Tasaduq, Yeary, Brian, Ndolo, Ruth, Bryant, Christina, Smigeil, Bridgette, Robinson, Philip, Najjar, Rana, Jones, Patrice, Nguyen, Julie, Chin, Christina, Taha, Hassan, Najm, Salah, Smith, Christopher, Moore, Jason, Nassar, Talal, Gallinger, Nick, Christian, Amy, Mauer, D’Amber, Phipps, Ashley, Waters, Michael, Zepeda, Karla, Coslet, Jordan, Landazuri, Rosalynn, Pineda, Jacob, Uribe, Nicole, Garcia, Jose Ruiz, Barbabosa, Cecilia, Sandler, Kaitlyn, Overcash, J. Scott, Marquez, Adrienna, Chu, Hanh, Lee, Kia, Quillin, Kimberly, Garcia, Andrea, Lew, Pauline, Rogers, Ralph, Shehadeh, Fadi, Mylona, Evangelia K., Kaczynski, Matthew, Tran, Quynh-Lam, Benitez, Gregorio, Mishra, Biswajit, Felix, Lewis Oscar, Vafea, Maria Tsikala, Atalla, Eleftheria, Davies, Robin, Hedili, Salma, Monkeberg, Maria Andrea, Tabler, Sandra, Harrington, Britt, Meegada, Sreenath, Koripalli, Venkata Sandeep, Muddana, Prithvi, Jain, Lakshay, Undavalli, Chaitanya, Kavya, Parasa, Ibiwoye, Mofoluwaso, Akilo, Hameed, Lovette, Bryce D., Wylie, Jamie-Crystal, Smith, Diana M., Poon, Kenneth, Eckardt, Paula, Heysu, Rubio-Gomez, Sundararaman, Nithya, Alaby, Doris, Sareli, Candice, Sánchez, Adriana, Popielski, Laura, Kambo, Amy, Viens, Kimberley, Turner, Melissa, Vjecha, Michael J., Weintrob, Amy, Brar, Indira, Markowitz, Norman, Pastor, Erika, Corpuz, Roweena, Alangaden, George, McKinnon, John, Ramesh, Mayur, Herc, Erica, Yared, Nicholas, Lanfranco, Odaliz Abreu, Rivers, Emanuel, Swiderek, Jennifer, Gupta, Ariella Hodari, Pabla, Pardeep, Eliya, Sonia, Jazrawi, Jehan, Delor, Jeremy, Desai, Mona, Cook, Aaron, Jaehne, Anja Kathrina, Gill, Jasreen Kaur, Renaud, Sheri, Sarveswaran, Siva, Gardner, Edward, Scott, James, Bianchini, Monica, Melvin, Casey, Kim, Gina, Wyles, David, Kamis, Kevin, Miller, Rachel, Douglas, Ivor, Haukoos, Jason, Hicks, Carrie, Lazarte, Susana, Marines-Price, Rubria, Osuji, Alice, Agbor Agbor, Barbine Tchamba, Petersen, Tianna, Kamel, Dena, Hansen, Laura, Garcia, Angie, Cha, Christine, Mozaffari, Azadeh, Hernandez, Rosa, Cutrell, James, Kim, Mina, DellaValle, Natalie, Gonzales, Sonia, Somboonwit, Charurut, Oxner, Asa, Guerra, Lucy, Hayes, Michael, Nguyen, Thi, Tran, Thanh, Pinto, Avenette, Hatlen, Timothy, Anderson, Betty, Zepeda-Gutierrez, Ana, Martin, Dannae, Temblador, Cindi, Cuenca, Avon, Tanoviceanu, Roxanne, Prieto, Martha, Guerrero, Mario, Daar, Eric, Correa, Ramiro, Hartnell, Gabe, Wortmann, Glenn, Doshi, Saumil, Moriarty, Theresa, Gonzales, Melissa, Garman, Kristin, Baker, Jason V., Frosch, Anne, Goldsmith, Rachael, Driver, Brian, Frank, Christine, Leviton, Tzivia, Prekker, Matthew, Jibrell, Hodan, Lo, Melanie, Klaphake, Jonathan, Mackedanz, Shari, Ngo, Linh, Garcia-Myers, Kelly, Kunisaki, Ken M., Wendt, Chris, Melzer, Anne, Wetherbee, Erin, Drekonja, Dimitri, Pragman, Alexa, Hamel, Aimee, Thielen, Abbie, Hassler, Miranda, Walquist, Mary, Augenbraun, Michael, George, Jensen, Demeo, Lynette, Mishko, Motria, Thomas, Lorraine, Tatem, Luis, Dehovitz, Jack, Abassi, Mahsa, Leuck, Anne-Marie, Rao, Via, Pullen, Matthew, Luke, Darlette, LaBar, Derek, Christiansen, Theresa, Howard, Diondra, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Davis-Karim, Anne, Pittman, David, Vasudeva, Shikha S., Johnstone, Jaylynn R., Agnetti, Kate, Davis, Ruby, Trautner, Barbara, Hines-Munson, Casey, Van, John, Dillon, Laura, Wang, Yiqun, Nagy-Agren, Stephanie, Vasudeva, Shikha, Ochalek, Tracy, Caldwell, Erin, Humerickhouse, Edward, Boone, David, McGraw, William, Looney, David J., Mehta, Sanjay R., Johns, Scott Thompson, St. John, Melissa, Raceles, Jacqueline, Sear, Emily, Funk, Stephen, Cesarini, Rosa, Fang, Michelle, Nicalo, Keith, Drake, Wonder, Jones, Beatrice, Holtman, Teresa, Nguyen, Hien H., Maniar, Archana, Johnson, Eric A., Nguyen, Lam, Tran, Michelle T., Barrett, Thomas W., Johnston, Tera, Huggins, John T., Beiko, Tatsiana Y., Hughes, Heather Y., McManigle, William C., Tanner, Nichole T., Washburn, Ronald G., Ardelt, Magdalena, Tuohy, Patricia A., Mixson, Jennifer L., Hinton, Charles G., Thornley, Nicola, Allen, Heather, Elam, Shannon, Boatman, Barry, Baber, Brittany J., Ryant, Rudell, Roller, Brentin, Nguyen, Chinh, Mikail, Amani Morgan, Research, Marivic Hansen, Lichtenberger, Paola, Baracco, Gio, Ramos, Carol, Bjork, Lauren, Sueiro, Melyssa, Tien, Phyllis, Freasier, Heather, Buck, Theresa, Nekach, Hafida, Holodniy, Mark, Chary, Aarthi, Lu, Kan, Peters, Theresa, Lopez, Jessica, Tan, Susanna Yu, Lee, Robert H., Asghar, Aliya, Karyn Isip, Tasadduq Karim, Le, Katherine, Nguyen, Thao, Wong, Shinn, Raben, Dorthe, Murray, Daniel D., Jensen, Tomas O., Peters, Lars, Aagaard, Bitten, Nielsen, Charlotte B., Krapp, Katharina, Nykjær, Bente Rosdahl, Olsson, Christina, Kanne, Katja Lisa, Grevsen, Anne Louise, Joensen, Zillah Maria, Bruun, Tina, Bojesen, Ane, Woldbye, Frederik, Normand, Nick E., Esman, Frederik V.L., Benfield, Thomas, Clausen, Clara Lundetoft, Hovmand, Nichlas, Israelsen, Simone Bastrup, Iversen, Katrine, Leding, Caecilie, Pedersen, Karen Brorup, Thorlacius-Ussing, Louise, Tinggaard, Michaela, Tingsgard, Sandra, Krohn-Dehli, Louise, Pedersen, Dorthe, Villadsen, Signe, Staehr Jensen, Jens-Ulrik, Overgaard, Rikke, Rastoder, Ema, Heerfordt, Christian, Hedsund, Caroline, Ronn, Christian Phillip, Kamstrup, Peter Thobias, Hogsberg, Dorthe Sandbaek, Bergsoe, Christina, Søborg, Christian, Hissabu, Nuria M.S., Arp, Bodil C., Ostergaard, Lars, Staerke, Nina Breinholt, Yehdego, Yordanos, Sondergaard, Ane, Johansen, Isik S., Pedersen, Andreas Arnholdt, Knudtzen, Fredrikke C., Larsen, Lykke, Hertz, Mathias A., Fabricius, Thilde, Holden, Inge K., Lindvig, Susan O., Helleberg, Marie, Gerstoft, Jan, Kirk, Ole, Jensen, Tomas Ostergaard, Madsen, Birgitte Lindegaard, Pedersen, Thomas Ingemann, Harboe, Zitta Barrella, Roge, Birgit Thorup, Hansen, Thomas Michael, Glesner, Matilde Kanstrup, Lofberg, Sandra Valborg, Nielsen, Ariella Denize, Leicht von Huth, Sebastian, Nielsen, Henrik, Thisted, Rikke Krog, Petersen, Kristine Toft, Juhl, Maria Ruwald, Podlekareva, Daria, Johnsen, Stine, Andreassen, Helle Frost, Pedersen, Lars, Clara Ellinor Lindnér, Cecilia Ebba, Wiese, Lothar, Knudsen, Lene Surland, Skrøder Nytofte, Nikolaj Julian, Havmøller, Signe Ravn, Expósito, Maria, Badillo, José, Martínez, Ana, Abad, Elena, Chamorro, Ana, Figuerola, Ariadna, Mateu, Lourdes, España, Sergio, Lucero, Maria Constanza, Santos, José Ramón, Lladós, Gemma, Lopez, Cristina, Carabias, Lydia, Molina-Morant, Daniel, Loste, Cora, Bracke, Carmen, Siles, Adrian, Fernández-Cruz, Eduardo, Di Natale, Marisa, Padure, Sergiu, Gomez, Jimena, Ausin, Cristina, Cervilla, Eva, Balastegui, Héctor, Sainz, Carmen Rodríguez, Lopez, Paco, Carbone, Javier, Escobar, Mariam, Balerdi, Leire, Legarda, Almudena, Roldan, Montserrat, Letona, Laura, Muñoz, José, Camprubí, Daniel, Arribas, Jose R., Sánchez, Rocio Montejano, Díaz-Pollán, Beatriz, Stewart, Stefan Mark, Garcia, Irene, Borobia, Alberto, Mora-Rillo, Marta, Estrada, Vicente, Cabello, Noemi, Nuñez-Orantos, M.J., Sagastagoitia, I., Homen, J.R., Orviz, E., Montalvá, Adrián Sánchez, Espinosa-Pereiro, Juan, Bosch-Nicolau, Pau, Salvador, Fernando, Burgos, Joaquin, Morales-Rull, Jose Luis, Moreno Pena, Anna Maria, Acosta, Cristina, Solé-Felip, Cristina, Horcajada, Juan P., Sendra, Elena, Castañeda, Silvia, López-Montesinos, Inmaculada, Gómez-Junyent, Joan, Gonzáles, Carlota Gudiol, Cuervo, Guilermo, Pujol, Miquel, Carratalà, Jordi, Videla, Sebastià, Günthard, Huldrych, Braun, Dominique L., West, Emily, M’Rabeth-Bensalah, Khadija, Eichinger, Mareile L., Grüttner-Durmaz, Manuela, Grube, Christina, Zink, Veronika, pharmacist, Goes pharmacist, Josefine, Fätkenheuer, Gerd, Malin, Jakob J., Tsertsvadze, Tengiz, Abutidze, Akaki, Chkhartishvili, Nikoloz, Metchurtchlishvili, Revaz, Endeladze, Marina, Paciorek, Marcin, Bursa, Dominik, Krogulec, Dominika, Pulik, Piotr, Ignatowska, Anna, Horban, Andrzej, Bakowska, Elzbieta, Kowaska, Justyna, Bednarska, Agnieszka, Jurek, Natalia, Skrzat-Klapaczynska, Agata, Bienkowski, Carlo, Hackiewicz, Malgorzata, Makowiecki, Michal, Platowski, Antoni, Fishchuk, Roman, Kobrynska, Olena, Levandovska, Khrystyna, Kirieieva, Ivanna, Kuziuk, Mykhailo, Naucler, Pontus, Perlhamre, Emma, Mazouch, Lotta, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina C., Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Young, Barnaby E., Chia, Po Ying, Lee, Tau Hong, Lin, Ray J., Lye, David C., Ong, Sean W.X., Puah, Ser Hon, Yeo, Tsin Wen, Diong, Shiau Hui, Ongko, Juwinda, Yeo, He Ping, Eriobu, Nnakelu, Kwaghe, Vivian, Zaiyad, Habib, Idoko, Godwin, Uche, Blessing, Selvamuthu, Poongulali, Kumarasamy, Nagalingeswaran, Beulah, Faith Ester, Govindarajan, Narayan, Mariyappan, Kowsalya, Losso, Marcelo H., Abela, Cecilia, Moretto, Renzo, Belloc, Carlos G., Ludueña, Jael, Amar, Josefina, Toibaro, Javier, Macias, Laura Moreno, Fernandez, Lucia, Frare, Pablo S., Chaio, Sebastian R., Pachioli, Valeria, Timpano, Stella M., Sanchez, Marisa del Lujan, de Paz Sierra, Mariana, Stanek, Vanina, Belloso, Waldo, Cilenti, Flavia L., Valentini, Ricardo N., Stryjewski, Martin E., Locatelli, Nicolas, Soler Riera, Maria C., Salgado, Clara, Baeck, Ines M., Di Castelnuovo, Valentina, Zarza, Stella M., Hudson, Fleur, Parmar, Mahesh K.B., Goodman, Anna L., Dphil, Badrock, Jonathan, Gregory, Adam, Goodall, Katharine, Harris, Nicola, Wyncoll, James, Bhagani, S., Rodger, A., Luntiel, A., Patterson, C., Morales, J., Witele, E., Preston, A.-M., Nandani, A., Price, D.A., Hanrath, Aiden, Nell, Jeremy, Patel, Bijal, Hays, Carole, Jones, Geraldine, Davidson, Jade, Bawa, T., Mathews, M., Mazzella, A., Bisnauthsing, K., Aguilar-Jimenez, L., Borchini, F., Hammett, S., Touloumi, Giota, Pantazis, Nikos, Gioukari, Vicky, Souliou, Tania, Antoniadou, A., Protopapas, K., Kavatha, D., Grigoropoulou, S., Oikonomopoulo, C., Moschopoulos, C., Koulouris, N.G., Tzimopoulos, K., Koromilias, A., Argyraki, K., Lourida, P., Bakakos, P., Kalomenidis, I., Vlachakos, V., Barmparessou, Z., Balis, E., Zakynthinos, S., Sigala, I., Gianniou, N., Dima, E., Magkouta, S., Synolaki, E., Konstanta, S., Vlachou, M., Stathopoulou, P., Panagopoulos, P., Petrakis, V., Papazoglou, D., Tompaidou, E., Isaakidou, E., Poulakou, G., Rapti, V., Leontis, K., Nitsotolis, T., Athanasiou, K., Syrigos, K., Kyriakoulis, K., Trontzas, I., Arfara-Melanini, M., Kolonis, V., Kityo, Cissy, Mugerwa, Henry, Kiweewa, Francis, Kimuli, Ivan, Lukaakome, Joseph, Nsereko, Christoher, Lubega, Gloria, Kibirige, Moses, Nakahima, William, Wangi, Deus, Aguti, Evelyne, Generous, Lilian, Massa, Rosemary, Nalaki, Margaret, Magala, Felix, Nabaggala, Phiona Kaweesi, Kidega, Robert, Faith, Oryem Daizy, Florence, Apio, Emmanuel, Ocung, Beacham, Mugoonyi Paul, Geoffrey, Amone, Nakiboneka, Dridah, Apiyo, Paska, Kirenga, Bruce, Atukunda, Angella, Muttamba, Winters, Remmy, Kyeyume, Segawa, Ivan, Pheona, Nsubuga, Kigere, David, Mbabazi, Queen Lailah, Boersalino, Ledra, Nyakoolo, Grace, Fred, Aniongo, Alupo, Alice, Ebong, Doryn, Monday, Edson, Nalubwama, Ritah Norah, Kainja, Milton, Ambrose, Munu, Kwehayo, Vanon, Nalubega, Mary Grace, Ongoli, Augustine, Obbo, Stephen, Sebudde, Nicholus, Alaba, Jeniffer, Magombe, Geoffrey, Tino, Harriet, Obonya, Emmanuel, Lutaakome, Joseph, Kitonsa, Jonathan, Onyango, Martin, Naboth, Tukamwesiga, Naluyinda, Hadijah, Nanyunja, Regina, Irene, Muttiibwa, Jane, Biira, Wimfred, Kyobejja, Leonard, Ssemazzi, Deus, Tkiinomuhisha, Babra, Namasaba, Taire, Paul, Nabankema, Evelyn, Ogavu, Joseph, Mugerwa, Oscar, Okoth, Ivan, Mwebaze, Raymond, Mugabi, Timothy, Makhoba, Anthony, Arikiriza, Phiona, Theresa, Nabuuma, Nakayima, Hope, Frank, Kisuule, Ramgi, Patrícia, Pereira, Kássia, Osinusi, Anu, Cao, Huyen, Klekotka, Paul, Price, Karen, Nirula, Ajay, Osei, Suzette, Tipple, Craig, Wills, Angela, Peppercorn, Amanda, Watson, Helen, Gupta, Rajesh, Alexander, Elizabeth, Mogalian, Erik, Lin, Leo, Ding, Xiao, Margolis, David, Yan, Li, Girardet, Jean-Luc, Ma, Ji, Hong, Zhi, Zhu, Quing, Seegobin, Seth, Gibbs, Michael, Latchman, Mickel, Hasior, Katarzyna, Bouquet, Jerome, Wei, Jianxin, Streicher, Katie, Schmelzer, Albert, Brooks, Dennis, Butcher, Jonny, Tonev, Dimitar, Arbetter, Douglas, Damstetter, Philippe, Legenne, Philippe, Stumpp, Michael, Goncalves, Susana, Ramanathan, Krishnan, Chandra, Richa, Baseler, Beth, Teitelbaum, Marc, Schechner, Adam, Holley, H. Preston, Jankelevich, Shirley, Becker, Nancy, Dolney, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Asomah, Mabel, Jato, Yvonne, Stottlemyer, April, Tang, Olivia, Vanderpuye, Sharon, Yeon, Lindsey, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonald, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Schaffhauser, Marylu, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, C.K., Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Kopka, Stacey, Shelley, Denise M., Mendez, Gregg, Brown, Shawn, Albert, Sara, Balde, Abby, Baracz, Michelle, Bielica, Mona, Billouin-Frazier, Shere, Choudary, Jay, Dixon, Mary, Eyler, Carolyn, Frye, Leanne, Gertz, Jensen, Giebeig, Lisa, Gulati, Neelam, Hankinson, Liz, Hogarty, Debi, Huber, Lynda, Krauss, Gary, Lake, Eileen, Manandhar, Meryan, Rudzinski, Erin, Sandrus, Jen, Suders, Connie, Natarajan, Ven, Rupert, Adam W., Baseler, Michael, Lynam, Danielle, Imamichi, Tom, Laverdure, Sylvain, McCormack, Ashley, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Khan, Ayub, Hazen, Allison, Badralmaa, Yunden, Smith, Kenneth, Patel, Bhakti, Kubernac, Amanda, Kubernac, Robert, Hoover, Marie L., Solomon, Courtney, Rashid, Marium, Murphy, Joseph, Brown, Craig, DuChateau, Nadine, Ellis, Sadie, Flosi, Adam, Fox, Lisa, Johnson, Les, Nelson, Rich, Stojanovic, Jelena, Treagus, Amy, Wenner, Christine, Williams, Richard, Jensen, Tomas O, Murray, Thomas A, Grandits, Greg A, Jain, Mamta K, Shaw-Saliba, Kathryn, Matthay, Michael A, Baker, Jason V, Dewar, Robin L, Goodman, Anna L, Hatlen, Timothy J, Highbarger, Helene C, Lallemand, Perrine, Leshnower, Bradley G, Looney, David, Moschopoulos, Charalampos D, Murray, Daniel D, Mylonakis, Eleftherios, Rehman, M Tauseef, Rupert, Adam, Stevens, Randy, Turville, Stuart, Wick, Katherine, Lundgren, Jens, and Ko, Emily R
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- 2024
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7. Effects of combination treatment with durvalumab plus tremelimumab on the tumor microenvironment in non-small-cell lung carcinoma
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Cheng, Li, Creasy, Todd, Pilataxi, Fernanda, Greenlees, Lydia, Vence, Luis, Sridhar, Sriram, and Streicher, Katie
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- 2022
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8. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial
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Abe, Wakana, Adan De Varona, Tania, Adiatullina, Daria, Aguilar Zapata, Daniel, Ahlers, Kevin, Aimo, Carolina, Akere, Ayoade, Akimova, Elena, Alatorre Alexander, Jorge, Aldrich, Logan, Ali Garcia, Ismael, Ali García, Karim, Allison, Lee, Alonso Zuñiga, Rosa, Aloysius, Ivan, Altclas, Javier, Alvarisqueta, Andres, Antila, Martti, Anton, Camila, Árboix Alamo, Elisabet, Arora, Samir, Avilés Felix, Ramón Alejandro, Bakhtina, Natalya, Barbero-Becerra, Varenka, Barragan-Reyes, Armando, Barreira, Alejandro, Barrett, Mitchell, Beran, Jiri, Berki, Nikolett, Berki, Viktoria, Betten, Richard, Binelli, Claudia, Brunzová, Lenka, Bussolari, Cecilia, Byargeon, Karianna, Bytnar, Justyna, Camberos, Carlos, Campos Corzo, Pedro, Cannon, Grazia, Canovi, Valentina, Carla da Rosa, Simone, Moser, Ana Caroline, Carrera Rivas, Luis, Casas, Marcelo Martin, Castañeda-Méndez, Paulo, Cavalcante, Ana, Cherepova, Eugenia, Chermenskii, Alexei, Clark, Lauren, Codeluppi, Mauro, Coelho, Flavia, Contreras, Belinda, Cran, Alex, Dao, Taylor, Dharma, Chrisette, Di Castri, Cosimo, Diaz Balocchi, Victoria, Durán, Omar, Earl, Kara, Ellery, Adam, Endo, Tomoko, Everding, Andrea, Fischer, Rainald, Fonseca, Benedito, Franklin, Chelsea C., Franz, Susan-Beatrice, Fumagalli, Anna, Galindo-Amaya, Mauricio, Galli, Mariagiulia, Gerna, Laura, Gil Ureña, Karolly, Gomes Antila, Henrikki, Gomes Maricato, Laura Ines, Goncalvez, Gabriela, Gonzalez, Martin, González-Lama, Jesús, Granier, Stephen, Granier, Jacob, Grunwald, Stephan, Guardeño-Ropero, David, Guberti, Monica, Guduri, Sridhar, Guerrero García, Carolina, Haggiagi, Jehad, Hale, Kacie, Hayashi, Toshimasa, Hermes, Maiara, Hernandez Colin, Dante, Hirai, Yuji, Hojo, Masayuki, Homma, Tetsuya, Hour, Billy, Huber, Andreas, Iacovelli, Diego, Ishibashi, Noriomi, Iwabe, Yutaro, Izumi, Shinyu, Jessen, Arne, Jessen, Heiko, Jeudy, Wilner, Jiménez Marcos, Marta, Johnson, Rebecca, Juárez-Hernández, Eva, Kabasawa, Kiyomi, Kamińska, Katarzyna, Kawabe, Megumi, Kemp, Angela, Khmelnitskiy, Oleg, Klassen, Carina, Kobrynska, Olena, Koleckar, Pavel, Korn, Stephanie, Kornmann, Marc, Kostenko, Viktor, Kovalchuk, Evgenii, Kovalchuk, Yana, Kümmerle, Tim, Lachmund, Ulrike, Lammersmann, Kerstin, Lastebasse, Flávio, Lattuada, Ivana, Lauer, Felicitas, Lebed, Kyrylo, Lebed, Olga, Lecona-Garcia, Diego, Leoni, Maria Christina, Lima, Marina, Little, Raymond, Little, Holly, Lizardi-Díaz, Andrea, Lobo-Becker, Michele, Luppi, Francesco, Macias, Veronica, Maesaki, Shigefumi, Magnaghi, Cristiano, Mancini, Annalisa, Mazur, Stanisław, Melnikova, Tatiana, Menchaca, Sergio, Menendez-Perez, Ibrahim, Międlar, Ewa, Mizunuma, Shuuichi, Mochalova, Anastasiya, Mohamed, Mihad, Moll, Theresa, Montalvo, Camila, Mottola, Amber, Mück, Birgit, Mussi Brugnolli, Rebeca, Nanda, Akanksha, Neuner, Dörthe, Ngwueke, Agatha, Noe, Sebastian, Novacek, Martin, Nuzzolo-Shihadeh, Laura, Obiekwe, Emeka, Ocampo Gaytán, Isaias G., Ohmagari, Norio, Ohta, Shin, Onyewuchi, Ptuonye, Pankov, Iurii, Pedrosa, Maurício, Peré, Yael, Pereyra, Alejandro, Perez, Eliana, Perez-Alba, Eduardo, Perpiña Lozano, Paloma, Perrei, Tanya, Peterson, Dena, Pierroti, Ligia, Pineda-Cárdenas, Felipe, Plascencia Sanchez, Teresa, Poletti, Camila, Pomaranzi, Chiara, Portes, Lisette, Postel, Nils, Ramirez, Monica, Ramírez, Isabel, Ramirez-Baena, Miguel, Ramjee, Mahadev, Ratti, Giovanna, Reeve, Jackie, Reichert, Petr, Reichertová, Petra, Reyes Garcia, Edgar Alejandro, Ricardo, Celso, Rodríguez Rodríguez, Nicomedes, Roldán Sánchez, Jaun, Romero-Lopez, Matilde, Rosales, Tyrone, Rosales, Harvey, Roshan, Mohamed, Roshan, Simran, Rovere Querini, Patrizia, Rutter, Heather, Sachwani, Sadaf, Sagara, Hironori, Sakai, Jun, Samson, Nina, Sánchez Mijangos, José Héctor, Sánchez, Liliana, Sánchez-González, Ana, Sandford, Micko, Santana, Laura, Santos de Carvalho, Felipe, Sasao, Reiko, Sato, Lubna, Scheuermann, Elizabeth, Schmidt, Olaf, Seki, Masafumi, Shaikh, Safia, Shimada, Daishi, Shinkai, Masaharu, Shinoda, Masahiro, Smith, Jackie, Solorzano, Fernando, Soncini, Silvia, Soregine, Katalin, Sosa, Erica, Sowade, Olalekan, Špinková, Veronika, Staniford, Ruth, Steigemann, Iska, Steiner, Vivien, Strelkov, Vladimir, Suárez Pineda, Cintya R., Suenaga, Hiroki, Suzaki, Shintaro, Swayze, Hannah, Tada, Yuji, Takeshita, Yuichiro, Takiguchi, Yasuo, Tanaka, Akihiko, Tarumoto, Norihito, Tatarintseva, Albina, Taubert, Michelle, Terenya, Elizaveta, Tinoco, César, Tomiyasu, Tomohiro, Torres-Vidal, Gladys, Trejo-Aguiar, Gabriela, Tsushima, Kenji, Tunstall, Emma, Turrà, Caterina, Valdes, Yoandy, Valencia Castro, Nelly, Visconti, Guilherme, Vitali, Giordano, Vutikullird, Apinya, Watti, Jezdancher, Werth, Doreen, Wilson, Cheyanne, Wilson, Philippe, Workman, Amy, Wörle, Pamela, Wyen, Christoph, Yamaguchi, Yoshiko, Yamamoto, Kei, Montgomery, Hugh, Hobbs, F D Richard, Padilla, Francisco, Arbetter, Douglas, Templeton, Alison, Seegobin, Seth, Kim, Kenneth, Campos, Jesus Abraham Simón, Arends, Rosalinda H, Brodek, Bryan H, Brooks, Dennis, Garbes, Pedro, Jimenez, Julieta, Koh, Gavin C K W, Padilla, Kelly W, Streicher, Katie, Viani, Rolando M, Alagappan, Vijay, Pangalos, Menelas N, and Esser, Mark T
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- 2022
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9. Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitroIC50 values predict SARS‐CoV‐2 neutralising antibody titres.
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Clegg, Lindsay E, Stepanov, Oleg, Matthews, Sam, White, Tom, Seegobin, Seth, Thomas, Steven, Tuffy, Kevin M, Någård, Mats, Esser, Mark T, Streicher, Katie, Cohen, Taylor S, and Aksyuk, Anastasia A
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SARS-CoV-2 ,ANTIBODY titer ,SARS-CoV-2 Omicron variant - Abstract
Objectives: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus‐neutralising antibody (nAb) titres in serum. However, authentic virus‐based assays pose inherent practical challenges for measuring nAb titres against emerging SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum. Methods: SARS‐CoV‐2 nAb titres were determined via authentic‐ and lentiviral pseudovirus‐based neutralisation assays using serological data from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose‐ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum‐based half‐maximal inhibitory concentration (IC50) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with in vitro IC50 measurements. Results: nAb titres measured via authentic‐ and lentiviral pseudovirus‐based neutralisation assays were strongly correlated for the ancestral SARS‐CoV‐2 virus and SARS‐CoV‐2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS‐CoV‐2 variants with all Spearman correlation coefficients ≥ 0.78. Serum‐based IC50 values were similar to in vitro IC50 values for AZD7442, for ancestral SARS‐CoV‐2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants. Conclusions: These data highlight that serum mAb concentrations and pseudovirus in vitro IC50 values can be used to rapidly predict nAb titres in serum for emerging and historical SARS‐CoV‐2 variants. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring
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Nicholson, Simone M., Carlesso, Gianluca, Cheng, Lily I., Cook, Halie, DaCosta, Karma, Leininger, Joel, McKeever, Kathleen, Scott, Stephen (Weasel), Taylor, Devon, Streicher, Katie, Eck, Steve, Reed, Molly, Faggioni, Raffaella, Herbst, Ronald, Dixit, Rakesh, and Ryan, Patricia C.
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- 2017
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11. Development and analytical performance of a new ARCHITECT automated dipeptidyl peptidase-4 immunoassay
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Hemken, Philip M., Jeanblanc, Nicolette M., Rae, Tracey, Brophy, Susan E., Datwyler, Maria J., Xu, Ying, Manetz, T. Scott, Vainshtein, Inna, Liang, Meina, Xiao, Xiaodong, Chowdhury, Partha S., Chang, Chien-ying, Streicher, Katie, Greenlees, Lydia, Ranade, Koustubh, and Davis, Gerard J.
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- 2017
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12. Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus
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Smith, Michael A., Chiang, Chia-Chien, Zerrouki, Kamelia, Rahman, Saifur, White, Wendy I., Streicher, Katie, Rees, William A., Schiffenbauer, Adam, Rider, Lisa G., Miller, Frederick W., Manna, Zerai, Hasni, Sarfaraz, Kaplan, Mariana J., Siegel, Richard, Sinibaldi, Dominic, Sanjuan, Miguel A., and Casey, Kerry A.
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- 2020
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13. Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants.
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Tuffy, Kevin M, Ahani, Bahar, Aksyuk, Anastasia A, Avila, Miles, Brady, Tyler, Kijak, Gustavo H, Koh, Gavin, Levin, Myron J, Roe, Tiffany L, Schuko, Nicolette, Thissen, Jesse, Ustianowski, Andrew, Zhang, Tianhui, Kelly, Elizabeth J, and Streicher, Katie
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SARS-CoV-2 ,BREAKTHROUGH infections ,INFECTION prevention ,COVID-19 ,CORONAVIRUS diseases ,CLINICAL trial registries - Abstract
Background We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial. Methods Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles. Results At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases. SARS-CoV-2 neutralizing antibody titers were similar in breakthrough and nonbreakthrough cases. Conclusions Symptomatic COVID-19 breakthrough cases in PROVENT were not due to resistance-associated substitutions in AZD7442 binding sites or lack of AZD7442 exposure. Clinical Trials Registration NCT04625725. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults.
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Forte-Soto, Pablo, Albayaty, Muna, Brooks, Dennis, Arends, Rosalinda H, Tillinghast, John, Aksyuk, Anastasia A, Bouquet, Jerome, Chen, Cecil, Gebre, Asfiha, Kubiak, Robert J, Reddy, Venkatesh Pilla, Seegobin, Seth, Streicher, Katie, Templeton, Alison, and Esser, Mark T
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SARS-CoV-2 ,MONOCLONAL antibodies ,CONVALESCENT plasma ,COVID-19 ,CLINICAL trial registries - Abstract
Background AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). Methods This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated AZD7442 administered intramuscularly (300 mg) or intravenously (300, 1000, or 3000 mg) in healthy adults (aged 18–55 years). The primary end point was safety and tolerability. Secondary end points included pharmacokinetics and antidrug antibodies. Results Between 18 August and 16 October 2020, a total of 60 participants were enrolled; 50 received AZD7442, and 10 received placebo. Adverse events (all of mild or moderate intensity) occurred in 26 participants (52.0%) in the AZD7442 groups and 8 (80.0%) in the placebo group. No infusion or injection site or hypersensitivity reactions occurred. Tixagevimab and cilgavimab had mean half-lives of approximately 90 days (range, 87.0–95.3 days for tixagevimab and 79.8–-91.1 days for cilgavimab) and similar pharmacokinetic profiles over the 361-day study period. SARS-CoV-2–specific neutralizing antibody titers provided by AZD7442 were maintained above those in plasma from convalescent patients with coronavirus disease 2019 (COVID-19). Conclusions AZD7442 was well tolerated in healthy adults, showing a favorable safety profile across all doses. Depending on the SARS-CoV-2 variant, pharmacokinetic analyses suggest the AZD7442 could offer protection for ≥6 months against symptomatic COVID-19 after a single 300-mg intramuscular administration. Clinical trials registration NCT04507256. [ABSTRACT FROM AUTHOR]
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- 2023
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15. AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019.
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Levin, Myron J, Ustianowski, Andrew, Thomas, Steven, Templeton, Alison, Yuan, Yuan, Seegobin, Seth, Houlihan, Catherine F, Menendez-Perez, Ibrahim, Pollett, Simon, Arends, Rosalinda H, Beavon, Rohini, Dey, Kanika, Garbes, Pedro, Kelly, Elizabeth J, Koh, Gavin C K W, Ivanov, Stefan, Near, Karen A, Sharbaugh, Audrey, Streicher, Katie, and Pangalos, Menelas N
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THERAPEUTIC use of monoclonal antibodies ,REVERSE transcriptase polymerase chain reaction ,COVID-19 ,CONFIDENCE intervals ,TREATMENT effectiveness ,RANDOMIZED controlled trials ,DESCRIPTIVE statistics ,RESEARCH funding ,STATISTICAL sampling - Abstract
Background This phase 3 trial assessed AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis against symptomatic coronavirus disease 2019 (COVID-19). Methods Adults without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2–infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab) or placebo. Primary end points were safety and first post-dose SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR)–positive symptomatic COVID-19 event before day 183. Results A total of 1121 participants were randomized and dosed (AZD7442, n = 749; placebo, n = 372). Median (range) follow-up was 49 (5–115) and 48 (20–113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162 of 749 (21.6%) and 111 of 372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR–positive symptomatic COVID-19 occurred in 23 of 749 (3.1%) and 17 of 372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction, 33.3%; 95% confidence interval [CI], −25.9 to 64.7; P =.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR–negative (n = 974, 87%) or missing an RT-PCR result (n = 99, 9%) at baseline, AZD7442 reduced RT-PCR–positive symptomatic COVID-19 by 73.2% (95% CI, 27.1 to 90.1) vs placebo. Conclusions This study did not meet the primary efficacy end point of post-exposure prevention of symptomatic COVID-19. However, analysis of participants who were SARS-CoV-2 RT-PCR–negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19. Clinical Trials Registration. NCT04625972. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial.
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Montgomery, Hugh, Hobbs, F D Richard, Padilla, Francisco, Arbetter, Douglas, Templeton, Alison, Seegobin, Seth, Kim, Kenneth, Campos, Jesus Abraham Simón, Arends, Rosalinda H, Brodek, Bryan H, Brooks, Dennis, Garbes, Pedro, Jimenez, Julieta, Koh, Gavin C K W, Padilla, Kelly W, Streicher, Katie, Viani, Rolando M, Alagappan, Vijay, Pangalos, Menelas N, and Esser, Mark T
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COVID-19 treatment ,COVID-19 ,INTRAMUSCULAR injections ,ANTIGEN analysis ,COVID-19 vaccines - Abstract
Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov , NCT04723394. Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab–cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab–cilgavimab group and six in the placebo group. A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes. AstraZeneca. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Relationship Between Anifrolumab Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Moderate to Severe Systemic Lupus Erythematosus.
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Chia, Yen Lin, Tummala, Raj, Mai, Tu H., Rouse, Tomas, Streicher, Katie, White, Wendy I., Morand, Eric F., and Furie, Richard A.
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DRUG efficacy ,INTRAVENOUS therapy ,MONOCLONAL antibodies ,INTERFERONS ,DESCRIPTIVE statistics ,SYSTEMIC lupus erythematosus ,SECONDARY analysis - Abstract
This study aimed to elucidate the pharmacokinetic/pharmacodynamic and pharmacodynamic/efficacy relationships of anifrolumab, a type I interferon receptor antibody, in patients with moderate to severe systemic lupus erythematosus. Data were pooled from the randomized, 52‐week, placebo‐controlled TULIP‐1 and TULIP‐2 trials of intravenous anifrolumab (150 mg/300 mg, every 4 weeks for 48 weeks). Pharmacodynamic neutralization was measured with a 21‐gene type I interferon gene signature (21‐IFNGS) in patients with high IFNGS. The pharmacokinetic/pharmacodynamic relationship was analyzed graphically and modeled with a nonlinear mixed‐effects model. British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response rates were compared across 21‐IFNGS neutralization quartiles. Overall, 819 patients received ≥1 dose of anifrolumab or placebo, of whom 676 were IFNGS high. Over 52 weeks, higher average anifrolumab serum concentrations were associated with increased median 21‐IFNGS neutralization, which was rapid and sustained with anifrolumab 300 mg (>80%, weeks 12‐52), lower and delayed with anifrolumab 150 mg (>50%, week 52), and minimal with placebo. The proportion of patients with week 24 anifrolumab trough concentration exceeding the IC80 (3.88 μg/mL) was greater with anifrolumab 300 mg vs anifrolumab 150 mg (≈83% vs ≈27%), owing to the higher estimated median trough concentration (15.6 vs 0.2 μg/mL). BICLA response rates increased with 21‐IFNGS neutralization; more patients had a BICLA response in the highest vs lowest neutralization quartiles at week 52 (58.1% vs 37.6%). In conclusion, anifrolumab 300 mg every 4 weeks rapidly, substantially, and sustainably neutralized the 21‐IFNGS and was associated with clinical efficacy, supporting this dosing regimen in patients with systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials.
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Vital, Edward M., Merrill, Joan T., Morand, Eric F., Furie, Richard A., Bruce, Ian N., Yoshiya Tanaka, Manzi, Susan, Kalunian, Kenneth C., Kalyani, Rubana N., Streicher, Katie, Abreu, Gabriel, Tummala, Raj, and Tanaka, Yoshiya
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GLUCOCORTICOIDS ,RESEARCH ,CLINICAL trials ,RESEARCH methodology ,MONOCLONAL antibodies ,EVALUATION research ,INTERFERONS ,TREATMENT effectiveness ,COMPARATIVE studies ,BLIND experiment ,SYSTEMIC lupus erythematosus - Abstract
Objectives: To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.Methods: We performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.Results: In pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups.Conclusions: Overall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab.Trial Registration Number: NCT02446912, NCT02446899. [ABSTRACT FROM AUTHOR]- Published
- 2022
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19. Selenium inhibits 15-hydroperoxyoctadecadienoic acid-induced intracellular adhesion molecule expression in aortic endothelial cells
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Sordillo, Lorraine M., Streicher, Katie L., Mullarky, Isis K., Gandy, Jeffery C., Trigona, Wendy, and Corl, Chris M.
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- 2008
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20. Inhibition of Myogenic MicroRNAs 1, 133, and 206 by Inflammatory Cytokines Links Inflammation and Muscle Degeneration in Adult Inflammatory Myopathies
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Georgantas, Robert W., Streicher, Katie, Greenberg, Steven A., Greenlees, Lydia M., Zhu, Wei, Brohawn, Philip Z., Higgs, Brandon W., Czapiga, Meggan, Morehouse, Christopher A., Amato, Anthony, Richman, Laura, Jallal, Bahija, Yao, Yihong, and Ranade, Koustubh
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- 2014
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21. CYP3A5 genotypes affect tacrolimus pharmacokinetics and infectious complications in Chinese pediatric liver transplant patients
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Xue, Feng, Han, Longzhi, Chen, Yikuan, Xi, Zhifeng, Li, Qigen, Xu, Ning, Xia, Yun, Streicher, Katie, Zhang, Jianjun, and Xia, Qiang
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- 2014
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22. MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D
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Georgantas, Robert W., III, Streicher, Katie, Luo, Xiaobing, Greenlees, Lydia, Zhu, Wei, Liu, Zheng, Brohawn, Philip, Morehouse, Christopher, Higgs, Brandon W., Richman, Laura, Jallal, Bahija, Yao, Yihong, and Ranade, Koustubh
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- 2014
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23. The Plasma Cell Signature in Autoimmune Disease
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Streicher, Katie, Morehouse, Christopher A., Groves, Christopher J., Rajan, Bhargavi, Pilataxi, Fernanda, Lehmann, Kim P., Brohawn, Philip Z., Higgs, Brandon W., McKeever, Kathleen, Greenberg, Steven A., Fiorentino, David, Richman, Laura K., Jallal, Bahija, Herbst, Ronald, Yao, Yihong, and Ranade, Koustubh
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- 2014
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24. Mammary Gland Immunity and Mastitis Susceptibility
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Sordillo, Lorraine M. and Streicher, Katie L.
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- 2002
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25. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans.
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Loo, Yueh-Ming, McTamney, Patrick M., Arends, Rosalinda H., Abram, Michael E., Aksyuk, Anastasia A., Diallo, Seme, Flores, Daniel J., Kelly, Elizabeth J., Ren, Kuishu, Roque, Richard, Rosenthal, Kim, Streicher, Katie, Tuffy, Kevin M., Bond, Nicholas J., Cornwell, Owen, Bouquet, Jerome, Cheng, Lily I., Dunyak, James, Huang, Yue, and Rosenbaum, Anton I.
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COVID-19 ,MONOCLONAL antibodies ,IMMUNOGLOBULINS ,SARS-CoV-2 ,SARS-CoV-2 Delta variant ,CONVALESCENT plasma - Abstract
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19 and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from the lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300-mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained threefold above those of convalescent serum at 9 months after AZD7442 administration. About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19. Long-lasting antibodies: Although monoclonal antibody therapeutics have considerably improved outcomes for individuals with COVID-19, their utility as a prophylactic intervention is restricted by the emergence of variants of concern (VOCs) and by short half-lives. To address this, Loo et al. evaluated a pair of antibodies, collectively termed AZD7442, which bind to two distinct epitopes on the receptor binding domain of the SARS-CoV-2 spike protein and have been modified to have an extended half-life. The antibody combination protected nonhuman primates from infection with SARS-CoV-2 when administered prophylactically or therapeutically. The antibodies were also resistant to all tested VOC, including the delta variant. Last, the authors showed that AZD7442 administration to healthy adults resulted in neutralizing antibody titers that were projected to confer long-term protection. [ABSTRACT FROM AUTHOR]
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- 2022
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26. Genomic signatures characterize leukocyte infiltration in myositis muscles
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Zhu Wei, Streicher Katie, Shen Nan, Higgs Brandon W, Morehouse Chris, Greenlees Lydia, Amato Anthony A, Ranade Koustubh, Richman Laura, Fiorentino David, Jallal Bahija, Greenberg Steven A, and Yao Yihong
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Myositis ,Genomics ,Leukocyte infiltration ,Type 1 interferon ,miR-146a ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods In this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results Several gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of transcriptional changes in myositis muscle or other heterogeneous tissue samples. Taken together, the leukocyte index and other gene signatures developed in this study may be potential molecular biomarkers to help to further characterize inflammatory myopathies and aid in clinical development. These hypotheses need to be confirmed in separate and sufficiently powered clinical trials.
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- 2012
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27. Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI‐551) and Correlates With Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease
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Streicher, Katie, Sridhar, Sriram, Kuziora, Mike, Morehouse, Christopher A., Higgs, Brandon W., Sebastian, Yinong, Groves, Christopher J., Pilataxi, Fernanda, Brohawn, Philip Z., Herbst, Ronald, and Ranade, Koustubh
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THERAPEUTIC use of monoclonal antibodies , *ANTIGENS , *ATOPIC dermatitis , *BIOPSY , *DERMATOMYOSITIS , *PULMONARY emphysema , *GENES , *INTERSTITIAL lung diseases , *OBSTRUCTIVE lung diseases , *SYSTEMIC lupus erythematosus , *SYSTEMIC scleroderma , *SYMPTOMS , *SEVERITY of illness index , *MICROARRAY technology , *IDIOPATHIC pulmonary fibrosis - Abstract
Objective: B cells impact the progression of systemic sclerosis (SSc; scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. PC depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated the effects of PC depletion on SSc disease activity. Methods: A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase I clinical trials. We assessed microarray data from tissue from public studies of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic dermatitis, as well as blood from a phase IIb clinical trial in SLE. Results: The PC signature was elevated in SSc skin specimens compared to healthy donor skin (P = 2.28 × 10−6) and correlated with the baseline modified Rodnan skin thickness score (MRSS) (r = 0.64, P = 0.0004). Patients with a high PC signature at baseline showed greater improvement in the MRSS (mean ± SD change 35 ± 16%; P = 6.30 × 10−4) following anti‐CD19 treatment with inebilizumab (MEDI‐551) than did patients with a low PC signature at baseline (mean ± SD change 8 ± 12%; P = 0.104). The PC signature was overexpressed in tissue from patients with SLE, DM, COPD, interstitial lung disease, and IPF relative to controls (all fold change >2; P < 0.001). The PC signature also differed significantly between SLE patients with mild‐to‐moderate disease and those with severe disease (SLE Disease Activity Index cutoff at 10) (fold change 1.44; P = 3.90 × 10−3) and correlated significantly with the degree of emphysema in COPD (r = 0.53, P = 7.55 × 10−8). Conclusion: Our results support the notion that PCs have a role in the pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated pretreatment PC signature was associated with increased benefit from MEDI‐551 in SSc. [ABSTRACT FROM AUTHOR]
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- 2018
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28. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE.
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Shu Wang, Jingya Wang, Kumar, Varsha, Karnell, Jodi L., Naiman, Brian, Gross, Phillip S., Rahman, Saifur, Zerrouki, Kamelia, Hanna, Richard, Morehouse, Christopher, Holoweckyj, Nicholas, Hao Liu, Manna, Zerai, Goldbach-Mansky, Raphaela, Hasni, Sarfaraz, Siegel, Richard, Sanjuan, Miguel, Streicher, Katie, Cancro, Michael P., and Kolbeck, Roland
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INTERLEUKIN-21 ,B cells ,B cell differentiation ,PLASMA cells ,CELL differentiation ,CHEMOKINE receptors ,PROXIMAL kidney tubules ,IMMUNOGLOBULIN G - Abstract
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11c
hi T-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chi T-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11chi T-bet+ B cells in human SLE. [ABSTRACT FROM AUTHOR]- Published
- 2018
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29. Integrating Genomics into Drug Discovery and Development: Challenges and Aspirations.
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Raja, Rajiv, Lee, Young, Streicher, Katie, Conway, James, Wu, Song, Sridhar, Sriram, Kuziora, Mike, Liu, Hao, Higgs, Brandon, Brohawn, Philip, Bais, Carlos, Jallal, Bahija, and Ranade, Koustubh
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DRUG development ,EPIDERMAL growth factor receptors ,ANAPLASTIC lymphoma kinase ,NON-small-cell lung carcinoma ,GENETIC markers - Abstract
Molecular biomarkers are increasingly being used to identify subgroups of patients that have a higher chance of benefiting from targeted therapies. Identification of predictive biomarkers and development of companion diagnostics to accompany targeted agents have been shown to significantly improve the efficacy and approval rate of these novel therapies, making treatment decisions more personalized to individual patients. Mutations of epidermal growth factor receptor ( EGFR) and rearrangements of anaplastic lymphoma kinase ( ALK) in non-small-cell lung cancer and of BRAF in melanoma provide great examples of driver mutations defining patient subgroups that respond to specific therapeutic agents. Recent advances in genomic technologies such as next-generation sequencing offer new opportunities for discovery and development of targeted therapies. They also pose numerous challenges in implementing molecularly guided precision medicine in clinical care. In this article, we review how molecular diagnostics have evolved over recent decades, discuss types and capabilities of clinically applicable genomic technologies, and highlight examples of companion diagnostics that have gained regulatory approval. Finally, we discuss technical and regulatory challenges associated with incorporating next-generation genomic technologies into clinical practice and consider potential ways to overcome these challenges to enable precision medicine. [ABSTRACT FROM AUTHOR]
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- 2017
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30. Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study.
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Schiopu, Elena, Chatterjee, Soumya, Hsu, Vivien, Flor, Armando, Cimbora, Daniel, Patra, Kaushik, Wenliang Yao, Jing Li, Streicher, Katie, McKeever, Kathleen, White, Barbara, Katz, Eliezer, Drappa, Jorn, and Sweeny, Sarah
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- 2016
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31. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial.
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Brightling, Christopher E, Chanez, Pascal, Leigh, Richard, O'Byrne, Paul M, Korn, Stephanie, She, Dewei, May, Richard D, Streicher, Katie, Ranade, Koustubh, and Piper, Edward
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INTERLEUKIN-13 ,ASTHMA ,MONOCLONAL antibodies - Abstract
Summary Background Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma. Methods We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2b study at 98 sites in North America, South America, Europe, and Asia. Patients aged 18–75 years with severe asthma and two to six exacerbations in the previous year were randomly assigned (1:1), via an interactive voice-response or web-response system, to one of two dosing regimen groups (every 2 weeks, or every 2 weeks for 12 weeks then every 4 weeks) and further randomised (2:1), via computer-generated permuted-block randomisation (block size of six), to receive tralokinumab 300 mg or placebo for 1 year. All participants received high-dose fluticasone and salmeterol and continued other pre-study controller drugs. Treatment was administered by an unmasked study investigator not involved in the management of patients; all other study site personnel, patients, the study funder, and data analysts were masked to treatment allocation. The primary endpoint was the annual asthma exacerbation rate at week 52 in the intention-to-treat population. Key secondary endpoints included prebronchodilator forced expiratory volume in 1 s (FEV 1 ), Asthma Control Questionnaire-6 (ACQ-6), and Asthma Quality of Life Questionnaire–Standardised Version (AQLQ[S]). This trial is registered with ClinicalTrials.gov , number NCT01402986 . Findings Between Oct 4, 2011, and Feb 22, 2014, we randomly assigned 452 patients to receive placebo (n=151) or tralokinumab every 2 weeks (n=150) or every 4 weeks (n=151), of whom 383 (85%) completed the treatment period up to week 52. The annual asthma exacerbation rate at week 52 was similar between patients receiving tralokinumab every 2 weeks (0·91 per patient per year [95% CI 0·76–1·08]) and every 4 weeks (0·97 [0·81–1·14]), and those receiving placebo (0·90 [0·75–1·08]). At week 52, percentage changes in annual asthma exacerbation rate were not significant with tralokinumab every 2 weeks or every 4 weeks versus placebo (6% [95% CI −31 to 33; p=0·709] and −2% [–46 to 29; p=0·904], respectively), with positive changes showing a decrease in exacerbation rate and negative changes showing an increase. Prebronchodilator FEV 1 was significantly increased compared with placebo for tralokinumab every 2 weeks (change from baseline 7·3% [95% CI 2·6–12·0]; p=0·003), but not every 4 weeks (1·8% [–2·9 to 6·6]; p=0·448); however, we did not identify significant changes in the other key secondary endpoints. In a post-hoc subgroup analysis of patients not on long-term oral corticosteroids and with baseline FEV 1 reversibility of 12% or greater, we noted a non-significant improvement in asthma exacerbation rate (44% [95% CI −22 to 74]; p=0·147) and significant improvements in key secondary endpoints (FEV 1 12·2% [1·7–22·7]; p=0·022; ACQ-6 −0·55 [–1·07 to −0·04]; p=0·036; and AQLQ[S] 0·70 [0·12–1·28]; p=0·019) in patients given tralokinumab every 2 weeks (n=33) compared with placebo (n=48). In patients in this subgroup who also had baseline serum dipeptidyl peptidase-4 (DPP-4) higher than the population baseline median, we noted additional improvements in prebronchodilator FEV 1 , ACQ-6, and AQLQ(S), and, in those with periostin concentrations higher than the median, we noted improvements in asthma exacerbation rate, prebronchodilator FEV 1 , and ACQ-6. The incidence of treatment-emergent adverse events was similar between the tralokinumab and placebo groups. Treatment-emergent serious adverse events regarded as related to the study drug were pneumonia (one [1%] patient in the placebo group), pneumococcal pneumonia (one [1%] in the tralokinumab every 2 weeks group), angioedema (one [1%] in the placebo group), and worsening asthma (one [1%] in the tralokinumab every 2 weeks group and two [1%] in the tralokinumab every 4 weeks group). Interpretation In this phase 2b study, both tralokinumab regimens had an acceptable safety and tolerability profile but did not significantly reduce asthma exacerbation rates in patients with severe uncontrolled asthma. Improvement in FEV 1 with tralokinumab given every 2 weeks and results of post-hoc subgroup analyses suggested a possible treatment effect in a defined population of patients with severe uncontrolled asthma. This effect is being further investigated in ongoing phase 3 trials, along with the potential utility of DPP-4 and periostin as biomarkers of interleukin-13 pathway activation. Funding MedImmune. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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32. Micro RNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.
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Georgantas, Robert W., Streicher, Katie, Luo, Xiaobing, Greenlees, Lydia, Zhu, Wei, Liu, Zheng, Brohawn, Philip, Morehouse, Christopher, Higgs, Brandon W., Richman, Laura, Jallal, Bahija, Yao, Yihong, and Ranade, Koustubh
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TRANSGENE expression , *MELANOMA diagnosis , *MICRORNA , *MICROBIAL cell cycle , *BIOINFORMATICS , *TUMOR suppressor genes - Abstract
Expression profiling of micro RNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa-mi R-206 was down-regulated in melanoma (−75.4-fold, P = 1.7 × 10−4). Mi R-206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. Mi R-206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3′ UTR reporter gene assays revealed that mi R-206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa-mi R-206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa-mi R-206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as mi R-206 targets. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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33. Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower epithelial-mesenchymal transition signature and longer survival in squamous cell lung carcinoma.
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Liyan Jiang, Wei Zhu, Streicher, Katie, Morehouse, Chris, Brohawn, Philip, Xiaoxiao Ge, Zhengwei Dong, Xiaolu Yin Yin, Guanshan Zhu, Yi Gu, Ranade, Koustubh, Higgs, Brandon W., Yihong Yao, and Jiaqi Huang
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LUNG cancer patients ,INSULIN receptors ,MESENCHYMAL stem cells ,SQUAMOUS cell carcinoma ,EPITHELIAL cells ,MESSENGER RNA ,CANCER invasiveness - Abstract
Background To evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients. Methods RNA-seq data from 614 NSCLC [355 adenocarcinomas (LUAD) and 259 squamous cell carcinomas (LUSC) ] and 92 normal lung specimens were obtained from The Cancer Genome Atlas (TCGA) to evaluate the mRNA expression of insulin receptor isoform A (IR-A) and insulin receptor isoform B (IR-B). The differential expression status of the insulin receptor isoforms in NSCLC patients was confirmed using qRT-PCR assays with lung cancer cDNA arrays and primary tumor samples. Results The mRNA expression levels of IR-B were significantly lower in some NSCLC samples compared to normal lung specimens, including both LUAD and LUSC. Notably, no IR-B transcripts were detected - only the IR-A isoform was expressed in 11% of NSCLC patients. This decrease in IR-B expression contributed to an elevated IR-A/IR-B ratio, which was also associated with lower epithelial-mesenchymal transition gene signatures in NSCLC and longer patient survival under standard of care in LUSC. In addition to NSCLC, RNA-seq data from TCGA revealed a similar increase in IR-A/IR-B ratio in many other cancer types, with high prevalence in acute myeloid leukemia, glioblastoma multiforme, and brain lower grade glioma. Conclusions Our results indicate a common reduction of the mRNA expression level of IR-B and an increased IR-A/IR-B mRNA ratio in NSCLC and other tumor types. The relationship of altered IR-A/IR-B ratios with cancer progression and patient survival should be prospectively explored in future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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34. Genomic signatures characterize leukocyte infiltration in myositis muscles.
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Wei Zhu, Streicher, Katie, Nan Shen, Higgs, Brandon W., Morehouse, Chris, Greenlees, Lydia, Amato, Anthony A., Ranade, Koustubh, Richman, Laura, Fiorentino, David, Jallal, Bahija, Greenberg, Steven A., and Yihong Yao
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MUSCLE diseases , *INFLAMMATION , *BIOMARKERS , *MEDICAL experimentation on humans , *ANTINEOPLASTIC agents , *MESSENGER RNA - Abstract
Background: Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods: In this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results: Several gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions: Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of transcriptional changes in myositis muscle or other heterogeneous tissue samples. Taken together, the leukocyte index and other gene signatures developed in this study may be potential molecular biomarkers to help to further characterize inflammatory myopathies and aid in clinical development. These hypotheses need to be confirmed in separate and sufficiently powered clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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35. The Pathogenesis, Molecular Mechanisms, and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases.
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Ramaswamy, Madhu, Tummala, Raj, Streicher, Katie, Nogueira da Costa, Andre, and Brohawn, Philip Z.
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SYSTEMIC lupus erythematosus ,TYPE I interferons ,INTERFERON gamma ,AUTOIMMUNE diseases ,INTERFERONS - Abstract
Therapeutic success in treating patients with systemic lupus erythematosus (SLE) is limited by the multivariate disease etiology, multi-organ presentation, systemic involvement, and complex immunopathogenesis. Agents targeting B-cell differentiation and survival are not efficacious for all patients, indicating a need to target other inflammatory mediators. One such target is the type I interferon pathway. Type I interferons upregulate interferon gene signatures and mediate critical antiviral responses. Dysregulated type I interferon signaling is detectable in many patients with SLE and other autoimmune diseases, and the extent of this dysregulation is associated with disease severity, making type I interferons therapeutically tangible targets. The recent approval of the type I interferon-blocking antibody, anifrolumab, by the US Food and Drug Administration for the treatment of patients with SLE demonstrates the value of targeting this pathway. Nevertheless, the interferon pathway has pleiotropic biology, with multiple cellular targets and signaling components that are incompletely understood. Deconvoluting the complexity of the type I interferon pathway and its intersection with lupus disease pathology will be valuable for further development of targeted SLE therapeutics. This review summarizes the immune mediators of the interferon pathway, its association with disease pathogenesis, and therapeutic modalities targeting the dysregulated interferon pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
36. Transforming properties of TC-1 in human breast cancer: Interaction with FGFR2 and β-catenin signaling pathways.
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Yang, Zeng-Quan, Moffa, Allison B., Haddad, Ramsi, Streicher, Katie L., and Ethier, Stephen P.
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- 2007
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37. Thioredoxin Reductase Regulates Angiogenesis by Increasing Endothelial Cell-Derived Vascular Endothelial Growth Factor.
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Streicher, Katie L., Sylte, Matthew J., Johnson, Sally E., and Sordillo, Lorraine M.
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THIOREDOXIN , *ENZYMES , *NEOVASCULARIZATION , *VASCULAR endothelial growth factors , *CELL migration , *BREAST cancer , *CANCER chemoprevention - Abstract
Abstract: Low selenium (Se) status increases angiogenesis by inducing the production of vascular endothelial growth factor (VEGF); however, the mechanism responsible for VEGF up-regulation has yet to be characterized. Se's ability to control cellular oxidative state through its incorporation into selenoproteins such as thioredoxin reductase (TrxR) may explain previous studies that connect Se status to tumor angiogenesis. Therefore, the focus of this study was to determine if altered VEGF expression and angiogenesis due to decreased Se levels are influenced by reduced TrxR activity. We found that chemical inhibition of TrxR in Se-sufficient endothelial cells (ECs) was associated with increases in VEGF and VEGF receptor expression, cell migration, proliferation, and angiogenesis to levels similar to those seen in Se-deficient ECs. Specific inhibition of glutathione peroxidase did not affect pro-angiogenic responses, indicating a unique role of the TrxR system during low Se status. These data correlate changes in TrxR activity with changes in VEGF expression and angiogenic development in ECs, which is significant because minimal mechanistic data exist that explain the role of Se in cancer prevention. Understanding the importance of the tumor microenvironment in contributing to angiogenic regulation has the potential to significantly impact breast cancer chemoprevention strategies by focusing on maintaining proper EC function within the mammary gland. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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38. A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity.
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Karnell, Jodi L., Albulescu, Marius, Drabic, Stacey, Wang, Liangwei, Moate, Rachel, Baca, Manuel, Oganesyan, Vaheh, Gunsior, Michele, Thisted, Thomas, Yan, Li, Li, Jing, Xiong, Ximing, Eck, Steven C., de los Reyes, Melissa, Yusuf, Isharat, Streicher, Katie, Müller-Ladner, Ulf, Howe, David, Ettinger, Rachel, and Herbst, Ronald
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AUTOANTIBODIES ,AUTOIMMUNITY ,RHEUMATOID arthritis ,SCAFFOLD proteins ,IMMUNIZATION ,CELL differentiation ,IMMUNOGLOBULIN G - Abstract
VIB4920, a nonantibody scaffold protein, blocks CD40L and reduces autoantibodies and disease activity in patients with rheumatoid arthritis. Curbing CD40 signaling: The CD40 axis is a major collaborative mechanism of B and T cell responses. Previous attempts to disrupt this pathway to treat autoimmune disease led to adverse thrombotic events due to engagement of Fc receptors and platelet expression of CD40 ligand (CD40L). To avoid this issue, Karnell et al. designed a nonantibody scaffold protein, VIB4920, which blocks human CD40L. VIB4920 inhibits B cell activation but does not induce platelet aggregation in vitro. VIB4920 administration resulted in blunted responses to immunization in healthy people, and people with rheumatoid arthritis experienced reduced disease activity. No thrombotic side effects were encountered in either clinical trial. This next-generation therapeutic has the potential to be widely used to treat various autoimmune diseases. The CD40/CD40L axis plays a central role in the generation of humoral immune responses and is an attractive target for treating autoimmune diseases in the clinic. Here, we report the generation and clinical results of a CD40L binding protein, VIB4920, which lacks an Fc domain, therefore avoiding platelet-related safety issues observed with earlier monoclonal antibody therapeutics that targeted CD40L. VIB4920 blocked downstream CD40 signaling events, resulting in inhibition of human B cell activation and plasma cell differentiation, and did not induce platelet aggregation in preclinical studies. In a phase 1 study in healthy volunteers, VIB4920 suppressed antigen-specific IgG in a dose-dependent fashion after priming and boosting with the T-dependent antigen, KLH. Furthermore, VIB4920 significantly reduced circulating Ki67
+ dividing B cells, class-switched memory B cells, and a plasma cell gene signature after immunization. In a phase 1b proof-of-concept study in patients with rheumatoid arthritis, VIB4920 significantly decreased disease activity, achieving low disease activity or clinical remission in more than 50% of patients in the two higher-dose groups. Dose-dependent decreases in rheumatoid factor autoantibodies and Vectra DA biomarker score provide additional evidence that VIB4920 effectively blocked the CD40/CD40L pathway. VIB4920 demonstrated a good overall safety profile in both clinical studies. Together, these data demonstrate the potential of VIB4920 to significantly affect autoimmune disease and humoral immune activation and to support further evaluation of this molecule in inflammatory conditions. [ABSTRACT FROM AUTHOR]- Published
- 2019
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39. Development of a new ARCHITECT automated periostin immunoassay.
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Jeanblanc, Nicolette M., Hemken, Philip M., Datwyler, Maria J., Brophy, Susan E., Manetz, T. Scott, Lee, Rozanne, Liang, Meina, Chowdhury, Partha S., Varkey, Reena, Grant, Ethan P., Streicher, Katie, Greenlees, Lydia, Ranade, Koustubh, and Davis, Gerard J.
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ASTHMA diagnosis , *PERIOSTIN , *IMMUNOASSAY , *BIOMARKERS , *BLOOD serum analysis - Abstract
Background Periostin is being investigated as a potential biomarker for T-helper-2 (Th2)-driven asthma or eosinophilic inflammation and may help to identify patients more likely to benefit from interleukin-13-targeted treatments. We report the development and analytic performance of the investigational use only ARCHITECT Periostin Immunoassay, a new automated assay developed to detect serum periostin concentrations. Methods We assessed assay performance in terms of precision, sensitivity, linearity, interference from classical immunoassay interferents and representatives of common asthma medications, specimen handling, and isoform reactivity. The assay was also used to assess the biological variability of serum periostin concentrations in samples from healthy volunteers and from subjects with uncontrolled asthma (the intended use population). Results The percentage CVs for 5-day total precision, assessed using two instruments, was < 6% across 2 controls and one serum-based panel. Limit of quantitation was 4 ng/mL (dilution adjusted concentration), suiting the needs for this application. Dilution analysis yielded linear results and no endogenous sample or drug interferences were observed. All known periostin isoforms expressed in the mature human lung were detected by the assay. Conclusion Our studies provide support that the ARCHITECT Periostin Immunoassay is a reliable and robust test for measuring serum periostin concentrations. [ABSTRACT FROM AUTHOR]
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- 2017
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40. A whole genome transcriptional analysis of the early immune response induced by live attenuated and inactivated influenza vaccines in young children
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Zhu, Wei, Higgs, Brandon W., Morehouse, Chris, Streicher, Katie, Ambrose, Christopher S., Woo, Jennifer, Kemble, George W., Jallal, Bahija, and Yao, Yihong
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INFLUENZA vaccines , *GENOMICS , *MOLECULAR immune response , *VACCINATION of children , *CYTOKINES , *INTERFERONS , *BIOMARKERS , *GENE expression , *TRANSCRIPTION factors - Abstract
Abstract: The protective mechanisms of influenza vaccines in young children are not completely understood. A phase 2 clinical study was conducted in 85 children 12–35 months of age to describe and compare the immune responses to live attenuated influenza vaccine (LAIV) with trivalent inactivated influenza vaccine (TIV). To better understand the biology of vaccine effects, oligonucleotide microarrays were employed to measure the genome-wide changes in transcript profiles in whole blood at approximately 7 days after 1 dose of LAIV or TIV. Of the total 265 differentially expressed genes identified in this study, 6 clusters of genes were identified to be tightly coexpressed, many of which are likely modulated by cytokines including type 1 interferons (IFNs) and granulocyte–macrophage colony-stimulating factor. Additional functional analyses revealed that the type 1 IFN pathway and cell cycle regulation-related genes are enriched in the 6 coexpressed gene sets. Promoter characterization of these coexpressed genes also supported this conclusion. Moreover, it is suggested that the IFN-stimulated response element is likely to be a potential bidirectional promoter, and the CCAAT/enhancer-binding protein might cooperate with the E2F transcription factor family in the regulation of the cell cycle in the early immune response induced by the influenza vaccine. Overall, our study clearly indicates that the expression profile changes induced by LAIV are significantly different from those induced by TIV. These results suggest that the pattern of overexpression of type 1 IFN-stimulated genes can potentially be used as a biomarker to identify the early vaccination response of LAIV and may also explain, to a certain extent, previous clinical study observations of LAIV-induced protection against influenza-like illness in the first 2 weeks after administration. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
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