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1. CD98hc is a target for brain delivery of biotherapeutics

Author

Chew, Kylie S., Wells, Robert C., Moshkforoush, Arash, Chan, Darren, Lechtenberg, Kendra J., Tran, Hai L., Chow, Johann, Kim, Do Jin, Robles-Colmenares, Yaneth, Srivastava, Devendra B., Tong, Raymond K., Tong, Mabel, Xa, Kaitlin, Yang, Alexander, Zhou, Yinhan, Akkapeddi, Padma, Annamalai, Lakshman, Bajc, Kaja, Blanchette, Marie, Cherf, Gerald Maxwell, Earr, Timothy K., Gill, Audrey, Huynh, David, Joy, David, Knight, Kristen N., Lac, Diana, Leung, Amy Wing-Sze, Lexa, Katrina W., Liau, Nicholas P. D., Becerra, Isabel, Malfavon, Mario, McInnes, Joseph, Nguyen, Hoang N., Lozano, Edwin I., Pizzo, Michelle E., Roche, Elysia, Sacayon, Patricia, Calvert, Meredith E. K., Daneman, Richard, Dennis, Mark S., Duque, Joseph, Gadkar, Kapil, Lewcock, Joseph W., Mahon, Cathal S., Meisner, René, Solanoy, Hilda, Thorne, Robert G., Watts, Ryan J., Zuchero, Y. Joy Yu, and Kariolis, Mihalis S.

Published
2023
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2. Author Correction: CD98hc is a target for brain delivery of biotherapeutics

Author

Chew, Kylie S., Wells, Robert C., Moshkforoush, Arash, Chan, Darren, Lechtenberg, Kendra J., Tran, Hai L., Chow, Johann, Kim, Do Jin, Robles-Colmenares, Yaneth, Srivastava, Devendra B., Tong, Raymond K., Tong, Mabel, Xa, Kaitlin, Yang, Alexander, Zhou, Yinhan, Akkapeddi, Padma, Annamalai, Lakshman, Bajc, Kaja, Blanchette, Marie, Cherf, Gerald Maxwell, Earr, Timothy K., Gill, Audrey, Huynh, David, Joy, David, Knight, Kristen N., Lac, Diana, Leung, Amy Wing-Sze, Lexa, Katrina W., Liau, Nicholas P. D., Becerra, Isabel, Malfavon, Mario, McInnes, Joseph, Nguyen, Hoang N., Lozano, Edwin I., Pizzo, Michelle E., Roche, Elysia, Sacayon, Patricia, Calvert, Meredith E. K., Daneman, Richard, Dennis, Mark S., Duque, Joseph, Gadkar, Kapil, Lewcock, Joseph W., Mahon, Cathal S., Meisner, René, Solanoy, Hilda, Thorne, Robert G., Watts, Ryan J., Zuchero, Y. Joy Yu, and Kariolis, Mihalis S.

Published
2023
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3. Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic

Author

Logan, Todd, Simon, Matthew J, Rana, Anil, Cherf, Gerald M, Srivastava, Ankita, Davis, Sonnet S, Low, Ray Lieh Yoon, Chiu, Chi-Lu, Fang, Meng, Huang, Fen, Bhalla, Akhil, Llapashtica, Ceyda, Prorok, Rachel, Pizzo, Michelle E, Calvert, Meredith EK, Sun, Elizabeth W, Hsiao-Nakamoto, Jennifer, Rajendra, Yashas, Lexa, Katrina W, Srivastava, Devendra B, van Lengerich, Bettina, Wang, Junhua, Robles-Colmenares, Yaneth, Kim, Do Jin, Duque, Joseph, Lenser, Melina, Earr, Timothy K, Nguyen, Hoang, Chau, Roni, Tsogtbaatar, Buyankhishig, Ravi, Ritesh, Skuja, Lukas L, Solanoy, Hilda, Rosen, Howard J, Boeve, Bradley F, Boxer, Adam L, Heuer, Hilary W, Dennis, Mark S, Kariolis, Mihalis S, Monroe, Kathryn M, Przybyla, Laralynne, Sanchez, Pascal E, Meisner, Rene, Diaz, Dolores, Henne, Kirk R, Watts, Ryan J, Henry, Anastasia G, Gunasekaran, Kannan, Astarita, Giuseppe, Suh, Jung H, Lewcock, Joseph W, DeVos, Sarah L, and Di Paolo, Gilbert

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Rare Diseases, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), Neurodegenerative, Dementia, Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Biological Products, Bone Morphogenetic Proteins, Brain, Endosomes, Female, Frontotemporal Dementia, Gliosis, Humans, Induced Pluripotent Stem Cells, Inflammation, Lipid Metabolism, Lipofuscin, Lysosomal Storage Diseases, Lysosomes, Macrophages, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia, Nerve Degeneration, Phenotype, Progranulins, Receptors, Immunologic, Receptors, Transferrin, Tissue Distribution, GBA, LBPA, galectin-3, lipidomics, lipids, lipofuscin, lysobisphosphatidic acid, lysosome, metabolomics, neurodegenerative disease, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

GRN mutations cause frontotemporal dementia (GRN-FTD) due to deficiency in progranulin (PGRN), a lysosomal and secreted protein with unclear function. Here, we found that Grn-/- mice exhibit a global deficiency in bis(monoacylglycero)phosphate (BMP), an endolysosomal phospholipid we identified as a pH-dependent PGRN interactor as well as a redox-sensitive enhancer of lysosomal proteolysis and lipolysis. Grn-/- brains also showed an age-dependent, secondary storage of glucocerebrosidase substrate glucosylsphingosine. We investigated a protein replacement strategy by engineering protein transport vehicle (PTV):PGRN-a recombinant protein linking PGRN to a modified Fc domain that binds human transferrin receptor for enhanced CNS biodistribution. PTV:PGRN rescued various Grn-/- phenotypes in primary murine macrophages and human iPSC-derived microglia, including oxidative stress, lysosomal dysfunction, and endomembrane damage. Peripherally delivered PTV:PGRN corrected levels of BMP, glucosylsphingosine, and disease pathology in Grn-/- CNS, including microgliosis, lipofuscinosis, and neuronal damage. PTV:PGRN thus represents a potential biotherapeutic for GRN-FTD.

Published
2021

4. A TREM2-activating antibody with a blood–brain barrier transport vehicle enhances microglial metabolism in Alzheimer’s disease models

Author

van Lengerich, Bettina, Zhan, Lihong, Xia, Dan, Chan, Darren, Joy, David, Park, Joshua I., Tatarakis, David, Calvert, Meredith, Hummel, Selina, Lianoglou, Steve, Pizzo, Michelle E., Prorok, Rachel, Thomsen, Elliot, Bartos, Laura M., Beumers, Philipp, Capell, Anja, Davis, Sonnet S., de Weerd, Lis, Dugas, Jason C., Duque, Joseph, Earr, Timothy, Gadkar, Kapil, Giese, Tina, Gill, Audrey, Gnörich, Johannes, Ha, Connie, Kannuswamy, Malavika, Kim, Do Jin, Kunte, Sebastian T., Kunze, Lea H., Lac, Diana, Lechtenberg, Kendra, Leung, Amy Wing-Sze, Liang, Chun-Chi, Lopez, Isabel, McQuade, Paul, Modi, Anuja, Torres, Vanessa O., Nguyen, Hoang N., Pesämaa, Ida, Propson, Nicholas, Reich, Marvin, Robles-Colmenares, Yaneth, Schlepckow, Kai, Slemann, Luna, Solanoy, Hilda, Suh, Jung H., Thorne, Robert G., Vieira, Chandler, Wind-Mark, Karin, Xiong, Ken, Zuchero, Y. Joy Yu, Diaz, Dolo, Dennis, Mark S., Huang, Fen, Scearce-Levie, Kimberly, Watts, Ryan J., Haass, Christian, Lewcock, Joseph W., Di Paolo, Gilbert, Brendel, Matthias, Sanchez, Pascal E., and Monroe, Kathryn M.

Published
2023
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5. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma

Author

Maun, Henry R, Jackman, Janet K, Choy, David F, Loyet, Kelly M, Staton, Tracy L, Jia, Guiquan, Dressen, Amy, Hackney, Jason A, Bremer, Meire, Walters, Benjamin T, Vij, Rajesh, Chen, Xiaocheng, Trivedi, Neil N, Morando, Ashley, Lipari, Michael T, Franke, Yvonne, Wu, Xiumin, Zhang, Juan, Liu, John, Wu, Ping, Chang, Diana, Orozco, Luz D, Christensen, Erin, Wong, Manda, Corpuz, Racquel, Hang, Julie Q, Lutman, Jeff, Sukumaran, Siddharth, Wu, Yan, Ubhayakar, Savita, Liang, Xiaorong, Schwartz, Lawrence B, Babina, Magda, Woodruff, Prescott G, Fahy, John V, Ahuja, Rahul, Caughey, George H, Kusi, Aija, Dennis, Mark S, Eigenbrot, Charles, Kirchhofer, Daniel, Austin, Cary D, Wu, Lawren C, Koerber, James T, Lee, Wyne P, Yaspan, Brian L, Alatsis, Kathila R, Arron, Joseph R, Lazarus, Robert A, and Yi, Tangsheng

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Clinical Research, Asthma, Lung, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Respiratory, Adolescent, Allosteric Regulation, Animals, Antibodies, Monoclonal, Humanized, Cell Line, Female, Humans, Macaca fascicularis, Male, Mast Cells, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, SCID, Rabbits, Tryptases, allosteric protease inhibitor, anti-IgE, anti-tryptase, antibody engineering, asthma, mast cell, non-type 2 asthma, serine protease, tryptase, tryptase genetics, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a β-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.

Published
2019

6. Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic

Author

Logan, Todd, primary, Simon, Matthew J., additional, Rana, Anil, additional, Cherf, Gerald M., additional, Srivastava, Ankita, additional, Davis, Sonnet S., additional, Yoon Low, Ray Lieh, additional, Chiu, Chi-Lu, additional, Fang, Meng, additional, Huang, Fen, additional, Bhalla, Akhil, additional, Llapashtica, Ceyda, additional, Prorok, Rachel, additional, Pizzo, Michelle E., additional, Calvert, Meredith E.K., additional, Sun, Elizabeth W., additional, Hsiao-Nakamoto, Jennifer, additional, Rajendra, Yashas, additional, Lexa, Katrina W., additional, Srivastava, Devendra B., additional, van Lengerich, Bettina, additional, Wang, Junhua, additional, Robles-Colmenares, Yaneth, additional, Kim, Do Jin, additional, Duque, Joseph, additional, Lenser, Melina, additional, Earr, Timothy K., additional, Nguyen, Hoang, additional, Chau, Roni, additional, Tsogtbaatar, Buyankhishig, additional, Ravi, Ritesh, additional, Skuja, Lukas L., additional, Solanoy, Hilda, additional, Rosen, Howard J., additional, Boeve, Bradley F., additional, Boxer, Adam L., additional, Heuer, Hilary W., additional, Dennis, Mark S., additional, Kariolis, Mihalis S., additional, Monroe, Kathryn M., additional, Przybyla, Laralynne, additional, Sanchez, Pascal E., additional, Meisner, Rene, additional, Diaz, Dolores, additional, Henne, Kirk R., additional, Watts, Ryan J., additional, Henry, Anastasia G., additional, Gunasekaran, Kannan, additional, Astarita, Giuseppe, additional, Suh, Jung H., additional, Lewcock, Joseph W., additional, DeVos, Sarah L., additional, and Di Paolo, Gilbert, additional

Published
2024
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8. An anti-CD3/anti–CLL-1 bispecific antibody for the treatment of acute myeloid leukemia

Author

Leong, Steven R., Sukumaran, Siddharth, Hristopoulos, Maria, Totpal, Klara, Stainton, Shannon, Lu, Elizabeth, Wong, Alfred, Tam, Lucinda, Newman, Robert, Vuillemenot, Brian R., Ellerman, Diego, Gu, Chen, Mathieu, Mary, Dennis, Mark S., Nguyen, Allen, Zheng, Bing, Zhang, Crystal, Lee, Genee, Chu, Yu-Waye, Prell, Rodney A., Lin, Kedan, Laing, Steven T., and Polson, Andrew G.

Published
2017
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9. Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation

Author

Liao, Fan, Li, Aimin, Xiong, Monica, Bien-Ly, Nga, Jiang, Hong, Zhang, Yin, Finn, Mary Beth, Hoyle, Rosa, Keyser, Jennifer, Lefton, Katheryn B., Robinson, Grace O., Serrano, Javier Remolina, Silverman, Adam P., Guo, Jing L., Getz, Jennifer, Henne, Kirk, Leyns, Cheryl E.G., Gallardo, Gilbert, Ulrich, Jason D., Sullivan, Patrick M., Lerner, Eli Paul, Hudry, Eloise, Sweeney, Zachary K., Dennis, Mark S., Hyman, Bradley T., Watts, Ryan J., and Holtzman, David M.

Subjects
Medical research, Apolipoproteins -- Health aspects -- Physiological aspects, Antibodies -- Research, Alzheimer's disease -- Development and progression -- Prevention, Amyloid beta-protein -- Health aspects -- Physiological aspects, Health care industry
Abstract

The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid [beta] (A[beta]) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease A[beta] pathology in mice producing both human A[beta] and apoE4, and investigated the mechanism underlying these effects. We utilized APPPS1-21 mice crossed to apoE4-knockin mice expressing human apoE4 (APPPS1-21/APOE4). We discovered an anti-human apoE antibody, anti-human apoE 4 (HAE-4), that specifically recognizes human apoE4 and apoE3 and preferentially binds nonlipidated, aggregated apoE over the lipidated apoE found in circulation. HAE-4 also binds to apoE in amyloid plaques in unfixed brain sections and in living APPPS1-21/APOE4 mice. When delivered centrally or by peripheral injection, HAE-4 reduced A| deposition in APPPS1-21/APOE4 mice. Using adeno-associated virus to express 2 different full-length anti-apoE antibodies in the brain, we found that HAE antibodies decreased amyloid accumulation, which was dependent on Fc[gamma] receptor function. These data support the hypothesis that a primary mechanism for apoE-mediated plaque formation may be a result of apoE aggregation, as preferentially targeting apoE aggregates with therapeutic antibodies reduces A[beta] pathology and may represent a selective approach to treat AD., Introduction Alzheimer disease (AD) is the most common form of dementia and it affects more than 5 million people in the United States (www.alz. org). Compelling evidence has shown that [...]

Published
2018
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10. Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier

Author

Barker, Scarlett J, primary, Thayer, Mai B, additional, Kim, Chaeyoung, additional, Tatarakis, David, additional, Simon, Matthew, additional, Dial, Rebekah L, additional, Nilewski, Lizanne, additional, Wells, Robert C, additional, Zhou, Yinhan, additional, Afetian, Megan, additional, Chappell, Alfred, additional, Chew, Kylie S, additional, Chow, Johann, additional, Clemens, Allisa, additional, Discenza, Claire B, additional, Dugas, Jason C, additional, Dwyer, Chrissa, additional, Earr, Timothy, additional, Ha, Connie, additional, Huynh, David, additional, Jayaraman, Srini, additional, Kwan, Wanda, additional, Mahon, Cathal, additional, Pizzo, Michelle, additional, Roche, Elysia, additional, Sanders, Laura, additional, Stergioulis, Alexander, additional, Tong, Raymond, additional, Tran, Hai, additional, Zuchero, Joy, additional, Estrada, Anthony A, additional, Gadkar, Kapil, additional, Koth, Christopher MM, additional, Sanchez, Pascal E, additional, Thorne, Robert G, additional, Watts, Ryan J, additional, Sandmann, Thomas, additional, Kane, Lesley A, additional, Rigo, Frank, additional, Dennis, Mark S, additional, Lewcock, Joseph W, additional, and DeVos, Sarah L, additional

Published
2023
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11. Data from An Anti-GDNF Family Receptor Alpha 1 (GFRA1) Antibody–Drug Conjugate for the Treatment of Hormone Receptor–Positive Breast Cancer

Author

Bhakta, Sunil, primary, Crocker, Lisa M., primary, Chen, Yvonne, primary, Hazen, Meredith, primary, Schutten, Melissa M., primary, Li, Dongwei, primary, Kuijl, Coenraad, primary, Ohri, Rachana, primary, Zhong, Fiona, primary, Poon, Kirsten A., primary, Go, Mary Ann T., primary, Cheng, Eric, primary, Piskol, Robert, primary, Firestein, Ron, primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Raab, Helga, primary, Hongo, Jo-Anne, primary, Sampath, Deepak, primary, Dennis, Mark S., primary, Scheller, Richard H., primary, Polakis, Paul, primary, and Junutula, Jagath R., primary

Published
2023
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12. Data from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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13. Data from Relative Target Affinities of T-Cell–Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model

Author

Mandikian, Danielle, primary, Takahashi, Nene, primary, Lo, Amy A., primary, Li, Ji, primary, Eastham-Anderson, Jeffrey, primary, Slaga, Dionysos, primary, Ho, Jason, primary, Hristopoulos, Maria, primary, Clark, Robyn, primary, Totpal, Klara, primary, Lin, Kedan, primary, Joseph, Sean B., primary, Dennis, Mark S., primary, Prabhu, Saileta, primary, Junttila, Teemu T., primary, and Boswell, C. Andrew, primary

Published
2023
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14. Supplemental Methods and Figures 1-5 from Relative Target Affinities of T-Cell–Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model

Author

Mandikian, Danielle, primary, Takahashi, Nene, primary, Lo, Amy A., primary, Li, Ji, primary, Eastham-Anderson, Jeffrey, primary, Slaga, Dionysos, primary, Ho, Jason, primary, Hristopoulos, Maria, primary, Clark, Robyn, primary, Totpal, Klara, primary, Lin, Kedan, primary, Joseph, Sean B., primary, Dennis, Mark S., primary, Prabhu, Saileta, primary, Junttila, Teemu T., primary, and Boswell, C. Andrew, primary

Published
2023
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15. Supplementary Table 1 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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16. Figures S1-S4, Tables S1-S2 from An Anti-GDNF Family Receptor Alpha 1 (GFRA1) Antibody–Drug Conjugate for the Treatment of Hormone Receptor–Positive Breast Cancer

Author

Bhakta, Sunil, primary, Crocker, Lisa M., primary, Chen, Yvonne, primary, Hazen, Meredith, primary, Schutten, Melissa M., primary, Li, Dongwei, primary, Kuijl, Coenraad, primary, Ohri, Rachana, primary, Zhong, Fiona, primary, Poon, Kirsten A., primary, Go, Mary Ann T., primary, Cheng, Eric, primary, Piskol, Robert, primary, Firestein, Ron, primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Raab, Helga, primary, Hongo, Jo-Anne, primary, Sampath, Deepak, primary, Dennis, Mark S., primary, Scheller, Richard H., primary, Polakis, Paul, primary, and Junutula, Jagath R., primary

Published
2023
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17. Supplementary Figure 3 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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18. Supplementary Table 2 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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19. Supplementary Figure 4 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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20. Supplementary Figure 2 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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21. Supplementary Materials and Methods and Supplementary Figure Legends from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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22. Supplementary Figure 1 from An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models

Author

Scales, Suzie J., primary, Gupta, Nidhi, primary, Pacheco, Glenn, primary, Firestein, Ron, primary, French, Dorothy M., primary, Koeppen, Hartmut, primary, Rangell, Linda, primary, Barry-Hamilton, Vivian, primary, Luis, Elizabeth, primary, Chuh, Josefa, primary, Zhang, Yin, primary, Ingle, Gladys S., primary, Fourie-O'Donohue, Aimee, primary, Kozak, Katherine R., primary, Ross, Sarajane, primary, Dennis, Mark S., primary, and Spencer, Susan D., primary

Published
2023
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23. Data from Antitumor Efficacy of a Bispecific Antibody That Targets HER2 and Activates T Cells

Author

Junttila, Teemu T., primary, Li, Ji, primary, Johnston, Jennifer, primary, Hristopoulos, Maria, primary, Clark, Robyn, primary, Ellerman, Diego, primary, Wang, Bu-Er, primary, Li, Yijin, primary, Mathieu, Mary, primary, Li, Guangmin, primary, Young, Judy, primary, Luis, Elizabeth, primary, Lewis Phillips, Gail, primary, Stefanich, Eric, primary, Spiess, Christoph, primary, Polson, Andrew, primary, Irving, Bryan, primary, Scheer, Justin M., primary, Junttila, Melissa R., primary, Dennis, Mark S., primary, Kelley, Robert, primary, Totpal, Klara, primary, and Ebens, Allen, primary

Published
2023
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24. Supplementary Figures 1-3 from Armed Antibodies Targeting the Mucin Repeats of the Ovarian Cancer Antigen, MUC16, Are Highly Efficacious in Animal Tumor Models

Author

Chen, Youjun, primary, Clark, Suzanna, primary, Wong, Terence, primary, Chen, Yongmei, primary, Chen, Yvonne, primary, Dennis, Mark S., primary, Luis, Elizabeth, primary, Zhong, Fiona, primary, Bheddah, Sheila, primary, Koeppen, Hartmut, primary, Gogineni, Alvin, primary, Ross, Sarajane, primary, Polakis, Paul, primary, and Mallet, William, primary

Published
2023
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25. Supplemental Figures 1 - 8 from Antitumor Efficacy of a Bispecific Antibody That Targets HER2 and Activates T Cells

Author

Junttila, Teemu T., primary, Li, Ji, primary, Johnston, Jennifer, primary, Hristopoulos, Maria, primary, Clark, Robyn, primary, Ellerman, Diego, primary, Wang, Bu-Er, primary, Li, Yijin, primary, Mathieu, Mary, primary, Li, Guangmin, primary, Young, Judy, primary, Luis, Elizabeth, primary, Lewis Phillips, Gail, primary, Stefanich, Eric, primary, Spiess, Christoph, primary, Polson, Andrew, primary, Irving, Bryan, primary, Scheer, Justin M., primary, Junttila, Melissa R., primary, Dennis, Mark S., primary, Kelley, Robert, primary, Totpal, Klara, primary, and Ebens, Allen, primary

Published
2023
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26. Data from Armed Antibodies Targeting the Mucin Repeats of the Ovarian Cancer Antigen, MUC16, Are Highly Efficacious in Animal Tumor Models

Author

Chen, Youjun, primary, Clark, Suzanna, primary, Wong, Terence, primary, Chen, Yongmei, primary, Chen, Yvonne, primary, Dennis, Mark S., primary, Luis, Elizabeth, primary, Zhong, Fiona, primary, Bheddah, Sheila, primary, Koeppen, Hartmut, primary, Gogineni, Alvin, primary, Ross, Sarajane, primary, Polakis, Paul, primary, and Mallet, William, primary

Published
2023
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27. Supplementary Figure Legends 1-3 from Armed Antibodies Targeting the Mucin Repeats of the Ovarian Cancer Antigen, MUC16, Are Highly Efficacious in Animal Tumor Models

Author

Chen, Youjun, primary, Clark, Suzanna, primary, Wong, Terence, primary, Chen, Yongmei, primary, Chen, Yvonne, primary, Dennis, Mark S., primary, Luis, Elizabeth, primary, Zhong, Fiona, primary, Bheddah, Sheila, primary, Koeppen, Hartmut, primary, Gogineni, Alvin, primary, Ross, Sarajane, primary, Polakis, Paul, primary, and Mallet, William, primary

Published
2023
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30. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent

Author

Merchant, Mark, Ma, Xiaolei, Maun, Henry R., Zheng, Zhong, Peng, Jing, Romero, Mally, Huang, Arthur, Yang, Nai-ying, Nishimura, Merry, Greve, Joan, Santell, Lydia, Zhang, Yu-Wen, Su, Yanli, Kaufman, Dafna W., Billeci, Karen L., Mai, Elaine, Moffat, Barbara, Lim, Amy, Duenas, Eileen T., Phillips, Heidi S., Xiang, Hong, Young, Judy C., Woude, George F. Vande, Dennis, Mark S., Reilly, Dorothea E., Schwall, Ralph H., Starovasnik, Melissa A., Lazarus, Robert A., and Yansura, Daniel G.

Published
2013

31. Molecular architecture determines brain delivery of a transferrin receptor–targeted lysosomal enzyme

Author

Arguello, Annie, primary, Mahon, Cathal S., additional, Calvert, Meredith E.K., additional, Chan, Darren, additional, Dugas, Jason C., additional, Pizzo, Michelle E., additional, Thomsen, Elliot R., additional, Chau, Roni, additional, Damo, Lorna A., additional, Duque, Joseph, additional, Fang, Meng, additional, Giese, Tina, additional, Kim, Do Jin, additional, Liang, Nicholas, additional, Nguyen, Hoang N., additional, Solanoy, Hilda, additional, Tsogtbaatar, Buyankhishig, additional, Ullman, Julie C., additional, Wang, Junhua, additional, Dennis, Mark S., additional, Diaz, Dolores, additional, Gunasekaran, Kannan, additional, Henne, Kirk R., additional, Lewcock, Joseph W., additional, Sanchez, Pascal E., additional, Troyer, Matthew D., additional, Harris, Jeffrey M., additional, Scearce-Levie, Kimberly, additional, Shan, Lu, additional, Watts, Ryan J., additional, Thorne, Robert G., additional, Henry, Anastasia G., additional, and Kariolis, Mihalis S., additional

Published
2022
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36. Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Author

Brightbill, Hans D., Jeet, Surinder, Lin, Zhonghua, Yan, Donghong, Zhou, Meijuan, Tan, Martha, Nguyen, Allen, Yeh, Sherry, Delarosa, Donnie, Leong, Steven R., Wong, Terence, Chen, Yvonne, Ultsch, Mark, Luis, Elizabeth, Ramani, Sree Ranjani, Jackman, Janet, Gonzalez, Lino, Dennis, Mark S., Chuntharapai, Anan, DeForge, Laura, Meng, Y. Gloria, Xu, Min, Eigenbrot, Charles, Lee, Wyne P., Refino, Canio J., Balazs, Mercedesz, and Wu, Lawren C.

Subjects
Cell physiology -- Research, Viral antibodies -- Properties -- Research, B cells -- Properties -- Research, Immunoglobulin E -- Properties -- Research, Antibodies -- Properties -- Research, Health care industry
Abstract

IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1' domain, and using genetically modified mice that contain the human M1' domain inserted into the mouse IgE locus, we demonstrated that M1'-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1'-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1'-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apopto-sis-inducing M1'-specific antibodies maybe a novel treatment for asthma and allergy., Introduction Elevated serum IgE levels and IgE-mediated hypersensitivity are central to the pathogenesis of atopic diseases such as allergic asthma (1-4). Elevated serum IgE levels cause the upregulation of IgE [...]

Published
2010
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37. Molecular architecture determines brain delivery of a transferrin-receptor targeted lysosomal enzyme

Author

Arguello, Annie, primary, Mahon, Cathal S., additional, Calvert, Meredith E. K., additional, Chan, Darren, additional, Dugas, Jason C., additional, Pizzo, Michelle E., additional, Thomsen, Elliot R., additional, Chau, Roni, additional, Damo, Lorna A., additional, Duque, Joseph, additional, Earr, Timothy, additional, Fang, Meng, additional, Giese, Tina, additional, Kim, Do Jin, additional, Liang, Nicholas, additional, Lopez, Isabel A., additional, Nguyen, Hoang N., additional, Solanoy, Hilda, additional, Tsogtbaatar, Buyankhishig, additional, Ullman, Julie C., additional, Wang, Junhua, additional, Dennis, Mark S., additional, Diaz, Dolores, additional, Gunasekaran, Kannan, additional, Henne, Kirk R., additional, Lewcock, Joseph W., additional, Sanchez, Pascal E., additional, Troyer, Matthew D., additional, Harris, Jeffrey M., additional, Scearce-Levie, Kimberly, additional, Shan, Lu, additional, Watts, Ryan J., additional, Thorne, Robert G., additional, Henry, Anastasia G., additional, and Kariolis, Mihalis S., additional

Published
2021
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38. A brain penetrant progranulin biotherapeutic rescues lysosomal and inflammatory phenotypes in the brain of GRN knockout mice

Author

Logan, Todd, primary, DeVos, Sarah, additional, Simon, Matthew J., additional, Davis, Sonnet, additional, Wang, Junhua, additional, Low, Ray, additional, Huang, Fen, additional, Rajendra, Yashas, additional, Prorok, Rachel, additional, Sun, Elizabeth, additional, Rana, Anil, additional, Hsiao‐Nakamoto, Jennifer, additional, Mosesova, Sofia, additional, Zhu, Yuda, additional, Cherf, Gerald M., additional, Lengerich, Bettina, additional, Bhalla, Akhil, additional, Kim, Do Jin, additional, Chan, Darren, additional, Duque, Joseph, additional, Tran, Hai, additional, Lenser, Melina, additional, Nguyen, Hoang, additional, Chau, Roni, additional, Earr, Timothy, additional, Kariolis, Mihalis S., additional, Monroe, Kathryn M., additional, Sanchez, Pascal E., additional, Dennis, Mark S., additional, Henne, Kirk R., additional, Gunasekaran, Kannan, additional, Astarita, Giuseppe, additional, Watts, Ryan J., additional, Sweeney, Zachary K., additional, Lewcock, Joseph W., additional, Srivastava, Ankita, additional, and Di Paolo, Gilbert, additional

Published
2020
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39. Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy

Author

Johnson, Leisa, Huseni, Mahrukh, Smyczek, Tanya, Lima, Anthony, Yeung, Stacey, Cheng, Jason H., Molina, Rafael, Kan, David, De Mazière, Ann, Klumperman, Judith, Kasman, Ian, Zhang, Yin, Dennis, Mark S., Eastham-Anderson, Jeffrey, Jubb, Adrian M., Hwang, Olivia, Desai, Rupal, Schmidt, Maike, Nannini, Michelle A., Barck, Kai H., Carano, Richard A.D., Forrest, William F., Song, Qinghua, Chen, Daniel S., Naumovski, Louie, Singh, Mallika, Ye, Weilan, and Hegde, Priti S.

Published
2013
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41. A novel exosite on coagulation Factor VIIa and its molecular interactions with a new class of peptide inhibitors

Author

Roberge, Martin, Santell, Lydia, Dennis, Mark S., Eigenbrot, Charles, Dwyer, Mary A., and Lazarus, Robert A.

Subjects
Biochemistry -- Research, Molecules -- Research, Peptides -- Physiological aspects, Proteases -- Physiological aspects, Biological sciences, Chemistry
Abstract

Research has been conducted on the inhibitory peptides. The identification of these peptides that bind exosite on the protease domain of the coagulation Factor VIIa has been carried out.

Published
2001

42. Selection and characterization of a new class of peptide exosite inhibitors of coagulation Factor VIIa

Author

Dennis, Mark S., Roberge, Martin, Quan, Cliff, and Lazarus, Robert A.

Subjects
Biochemistry -- Research, Peptides -- Physiological aspects, Coagulation -- Analysis, Membrane proteins -- Physiological aspects, Thrombin -- Physiological aspects, Biological sciences, Chemistry
Abstract

Research has been conducted on the peptide inhibitors of human Factor VII. The identification of these peptides has been performed and the results indicate that the affinity has matured from the naive and partially randomized peptide phage libraries.

Published
2001

44. Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys

Author

Kariolis, Mihalis S., primary, Wells, Robert C., additional, Getz, Jennifer A., additional, Kwan, Wanda, additional, Mahon, Cathal S., additional, Tong, Raymond, additional, Kim, Do Jin, additional, Srivastava, Ankita, additional, Bedard, Catherine, additional, Henne, Kirk R., additional, Giese, Tina, additional, Assimon, Victoria A., additional, Chen, Xiaocheng, additional, Zhang, Yin, additional, Solanoy, Hilda, additional, Jenkins, Katherine, additional, Sanchez, Pascal E., additional, Kane, Lesley, additional, Miyamoto, Takashi, additional, Chew, Kylie S., additional, Pizzo, Michelle E., additional, Liang, Nicholas, additional, Calvert, Meredith E. K., additional, DeVos, Sarah L., additional, Baskaran, Sulochanadevi, additional, Hall, Sejal, additional, Sweeney, Zachary K., additional, Thorne, Robert G., additional, Watts, Ryan J., additional, Dennis, Mark S., additional, Silverman, Adam P., additional, and Zuchero, Y. Joy Yu, additional

Published
2020
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45. Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice

Author

Ullman, Julie C., primary, Arguello, Annie, additional, Getz, Jennifer A., additional, Bhalla, Akhil, additional, Mahon, Cathal S., additional, Wang, Junhua, additional, Giese, Tina, additional, Bedard, Catherine, additional, Kim, Do Jin, additional, Blumenfeld, Jessica R., additional, Liang, Nicholas, additional, Ravi, Ritesh, additional, Nugent, Alicia A., additional, Davis, Sonnet S., additional, Ha, Connie, additional, Duque, Joseph, additional, Tran, Hai L., additional, Wells, Robert C., additional, Lianoglou, Steve, additional, Daryani, Vinay M., additional, Kwan, Wanda, additional, Solanoy, Hilda, additional, Nguyen, Hoang, additional, Earr, Timothy, additional, Dugas, Jason C., additional, Tuck, Michael D., additional, Harvey, Jennifer L., additional, Reyzer, Michelle L., additional, Caprioli, Richard M., additional, Hall, Sejal, additional, Poda, Suresh, additional, Sanchez, Pascal E., additional, Dennis, Mark S., additional, Gunasekaran, Kannan, additional, Srivastava, Ankita, additional, Sandmann, Thomas, additional, Henne, Kirk R., additional, Thorne, Robert G., additional, Di Paolo, Gilbert, additional, Astarita, Giuseppe, additional, Diaz, Dolores, additional, Silverman, Adam P., additional, Watts, Ryan J., additional, Sweeney, Zachary K., additional, Kariolis, Mihalis S., additional, and Henry, Anastasia G., additional

Published
2020
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46. Target arm affinities determine preclinical efficacy and safety of anti-HER2/CD3 bispecific antibody

Author

Staflin, Karin, primary, Zuch de Zafra, Christina L., additional, Schutt, Leah K., additional, Clark, Vanessa, additional, Zhong, Fiona, additional, Hristopoulos, Maria, additional, Clark, Robyn, additional, Li, Ji, additional, Mathieu, Mary, additional, Chen, Xiaocheng, additional, Johnston, Jennifer, additional, Low, Justin, additional, Ybarra, Ryan, additional, Slaga, Dionysos, additional, Yang, Jihong, additional, Ovacik, Meric, additional, Dybdal, Noël O., additional, Totpal, Klara, additional, Junttila, Melissa R., additional, Ellerman, Diego, additional, Lee, Genee, additional, Dennis, Mark S., additional, Prell, Rodney, additional, and Junttila, Teemu T., additional

Published
2020
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47. An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma

Author

Maun, Henry R., primary, Jackman, Janet K., additional, Choy, David F., additional, Loyet, Kelly M., additional, Staton, Tracy L., additional, Jia, Guiquan, additional, Dressen, Amy, additional, Hackney, Jason A., additional, Bremer, Meire, additional, Walters, Benjamin T., additional, Vij, Rajesh, additional, Chen, Xiaocheng, additional, Trivedi, Neil N., additional, Morando, Ashley, additional, Lipari, Michael T., additional, Franke, Yvonne, additional, Wu, Xiumin, additional, Zhang, Juan, additional, Liu, John, additional, Wu, Ping, additional, Chang, Diana, additional, Orozco, Luz D., additional, Christensen, Erin, additional, Wong, Manda, additional, Corpuz, Racquel, additional, Hang, Julie Q., additional, Lutman, Jeff, additional, Sukumaran, Siddharth, additional, Wu, Yan, additional, Ubhayakar, Savita, additional, Liang, Xiaorong, additional, Schwartz, Lawrence B., additional, Babina, Magda, additional, Woodruff, Prescott G., additional, Fahy, John V., additional, Ahuja, Rahul, additional, Caughey, George H., additional, Kusi, Aija, additional, Dennis, Mark S., additional, Eigenbrot, Charles, additional, Kirchhofer, Daniel, additional, Austin, Cary D., additional, Wu, Lawren C., additional, Koerber, James T., additional, Lee, Wyne P., additional, Yaspan, Brian L., additional, Alatsis, Kathila R., additional, Arron, Joseph R., additional, Lazarus, Robert A., additional, and Yi, Tangsheng, additional

Published
2020
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48. Peptide exosite inhibitors of factor VIIa as anticoagulants

Author

Dennis, Mark S., Eigenbrot, Charles, Skelton, Nicholas J., Ultsch, Mark H., Santell, Lydia, Dwyer, Mary A., O'Connell, Mark P., and Lazarus, Robert A.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Mark S. Dennis; Charles Eigenbrot; Nicholas J. Skelton; Mark H. Ultsch; Lydia Santell; Mary A. Dwyer [1]; Mark P. O'Connell; Robert A. Lazarus (corresponding author) Initiation of the extrinsic [...]

Published
2000
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50. Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor Xa

Author

Seymour, Jana L., Lindquist, Robert N., Dennis, Mark S., Moffat, Barbara, Yansura, Daniel, Reilly, Dorothea, Wessinger, Mary E., and Lazarus, Robert A.

Subjects
Proteases -- Research, Anticoagulants (Medicine) -- Analysis, Biological sciences, Chemistry
Abstract

The periplasm of E. coli contains a serine protease inhibitor called ecotin that is an anticoagulant and reversible tight-binding inhibitor of human factor Xa (FXa). The dissociation rate constant of the inhibitor is measured using human leukocyte elastase. Coincubation of FXa and ecotin produces an (ecotin)2. (FXa)2 structure. Fluorescence titration is used to analyze dimerization of ecotin.

Published
1994

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