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8. IM-07 * NK CELL IMMUNOTHERAPY FOR PEDIATRIC BRAIN TUMORS: OVERCOMING RESISTANCE TO EXPAND THERAPEUTIC SUCCESS

Author

Brugmann, W., primary, Laureano, A., additional, Michel, K., additional, Tao, R.-H., additional, Kennis, B., additional, Somanchi, S., additional, Denman, C., additional, Ho, K. C., additional, Silla, L., additional, Singh, H., additional, Huls, H., additional, Sandberg, D., additional, Lee, D., additional, Bankson, J., additional, Huang, A., additional, Cooper, L., additional, and Gopalakrishnan, V., additional

Published
2015
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9. PET imaging of T cells derived from umbilical cord blood

Author

Simmons, P.J., Huls, H., Manuri, P.R., Singh, H., Bollard, C., Gelovani, J.G., Najjar, A.M., Olivares, S., Shpall, E.J., Lee, D.A., Nishii, R., Alauddin, M., Mukhopadhyay, U., Champlin, R.E., Dotti, G., and Cooper, L.J.N.

Abstract

Progress in understanding tumor-specific immune responses, genetic engineering and ex vivo manufacturing, have led to improvements in the safety and feasibility of adoptive transfer of genetically modified T cells. However, rational design, application and evaluation of T-cell therapy requires monitoring methods that can detect, locate and serially quantify these cell-mediated immune responses. Currently, such monitoring methods are chiefly limited to invasive techniques to investigate recovered cell populations for in vitro measurements including histology, flow cytometry, Q-PCR or the detection of cytokines. These assays provide episodic glimpses of the bio distribution of T cells and are limited by the number and sites of sampling. In contrast, imaging provides a methodology for quantitative, non-invasive, longitudinal and spatial in vivo information about the dynamic processes of infused T cells.

Published
2009
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10. Financiering : van MKB tot grootbedrijf

Author

Huls, H. M. P. and Huls, H. M. P.

Subjects
Business enterprises--Finance
Abstract

In Financiering - van MKB tot grootbedrijf wordt de theorie steeds gekoppeld aan de beroepspraktijk. Net als in de andere twee delen van de Serie Financieel economische adviespraktijk. Onderwerpen die aan bod komen zijn o.a. kasstromen, investeringsselecties, werkkapitaalmanagement, bijzondere vermogensaantrekkingsaspecten en balansbeoordeling. Verder worden er ook nog meer specifieke onderwerpen uitgebreid behandeld, zoals fusies en overnames, pensioenvorming, export en het begeleiden van ondernemers bij kredietaanvragen/gesprekken. Een brede kennis van bedrijfseconomie is gewenst. Vervolgens kun je zelfstandig met de Serie Adviespraktijk in het MKB aan het werk. Aan de hand van de opgaven met uitwerkingen kun je je kennis steeds toetsen. Samen met de andere twee delen krijg je zo alle stof die nodig is voor accountancy. De Serie'Financieel economische adviespraktijk'vormt een compleet naslagwerk voor met name de hoofdfase van de Bedrijfseconomie en Accountancy opleidingen. De Serie bestaat uit drie boeken: Financiering, Management accounting en management control en Strategisch management.

Published
2010

11. MEDULLOBLASTOMA

Author

Vaidyanathan, G., primary, Gururangan, S., additional, Bigner, D., additional, Zalutsky, M., additional, Morfouace, M., additional, Shelat, A., additional, Megan, J., additional, Freeman, B. B., additional, Robinson, S., additional, Throm, S., additional, Olson, J. M., additional, Li, X.-N., additional, Guy, K. R., additional, Robinson, G., additional, Stewart, C., additional, Gajjar, A., additional, Roussel, M., additional, Sirachainan, N., additional, Pakakasama, S., additional, Anurathapan, U., additional, Hansasuta, A., additional, Dhanachai, M., additional, Khongkhatithum, C., additional, Hongeng, S., additional, Feroze, A., additional, Lee, K.-S., additional, Gholamin, S., additional, Wu, Z., additional, Lu, B., additional, Mitra, S., additional, Cheshier, S., additional, Northcott, P., additional, Lee, C., additional, Zichner, T., additional, Lichter, P., additional, Korbel, J., additional, Wechsler-Reya, R., additional, Pfister, S., additional, Project, I. P. T., additional, Li, K. K.-W., additional, Xia, T., additional, Ma, F. M. T., additional, Zhang, R., additional, Zhou, L., additional, Lau, K.-M., additional, Ng, H.-K., additional, Lafay-Cousin, L., additional, Chi, S., additional, Madden, J., additional, Smith, A., additional, Wells, E., additional, Owens, E., additional, Strother, D., additional, Foreman, N., additional, Packer, R., additional, Bouffet, E., additional, Wataya, T., additional, Peacock, J., additional, Taylor, M. D., additional, Ivanov, D., additional, Garnett, M., additional, Parker, T., additional, Alexander, C., additional, Meijer, L., additional, Grundy, R., additional, Gellert, P., additional, Ashford, M., additional, Walker, D., additional, Brent, J., additional, Cader, F. Z., additional, Ford, D., additional, Kay, A., additional, Walsh, R., additional, Solanki, G., additional, Peet, A., additional, English, M., additional, Shalaby, T., additional, Fiaschetti, G., additional, Baulande, S., additional, Gerber, N., additional, Baumgartner, M., additional, Grotzer, M., additional, Hayase, T., additional, Kawahara, Y., additional, Yagi, M., additional, Minami, T., additional, Kanai, N., additional, Yamaguchi, T., additional, Gomi, A., additional, Morimoto, A., additional, Hill, R., additional, Kuijper, S., additional, Lindsey, J., additional, Schwalbe, E., additional, Barker, K., additional, Boult, J., additional, Williamson, D., additional, Ahmad, Z., additional, Hallsworth, A., additional, Ryan, S., additional, Poon, E., additional, Ruddle, R., additional, Raynaud, F., additional, Howell, L., additional, Kwok, C., additional, Joshi, A., additional, Nicholson, S. L., additional, Crosier, S., additional, Wharton, S., additional, Robson, K., additional, Michalski, A., additional, Hargrave, D., additional, Jacques, T., additional, Pizer, B., additional, Bailey, S., additional, Swartling, F., additional, Petrie, K., additional, Weiss, W., additional, Chesler, L., additional, Clifford, S., additional, Kitanovski, L., additional, Prelog, T., additional, Kotnik, B. F., additional, Debeljak, M., additional, Grotzer, M. A., additional, Gevorgian, A., additional, Morozova, E., additional, Kazantsev, I., additional, Iukhta, T., additional, Safonova, S., additional, Kumirova, E., additional, Punanov, Y., additional, Afanasyev, B., additional, Zheludkova, O., additional, Grajkowska, W., additional, Pronicki, M., additional, Cukrowska, B., additional, Dembowska-Baginska, B., additional, Lastowska, M., additional, Murase, A., additional, Nobusawa, S., additional, Gemma, Y., additional, Yamazaki, F., additional, Masuzawa, A., additional, Uno, T., additional, Osumi, T., additional, Shioda, Y., additional, Kiyotani, C., additional, Mori, T., additional, Matsumoto, K., additional, Ogiwara, H., additional, Morota, N., additional, Hirato, J., additional, Nakazawa, A., additional, Terashima, K., additional, Fay-McClymont, T., additional, Walsh, K., additional, Mabbott, D., additional, Sturm, D., additional, Northcott, P. A., additional, Jones, D. T. W., additional, Korshunov, A., additional, Pfister, S. M., additional, Kool, M., additional, Hooper, C., additional, Hawes, S., additional, Kees, U., additional, Gottardo, N., additional, Dallas, P., additional, Siegfried, A., additional, Bertozzi, A. I., additional, Sevely, A., additional, Loukh, N., additional, Munzer, C., additional, Miquel, C., additional, Bourdeaut, F., additional, Pietsch, T., additional, Dufour, C., additional, Delisle, M. B., additional, Kawauchi, D., additional, Rehg, J., additional, Finkelstein, D., additional, Zindy, F., additional, Phoenix, T., additional, Gilbertson, R., additional, Trubicka, J., additional, Borucka-Mankiewicz, M., additional, Ciara, E., additional, Chrzanowska, K., additional, Perek-Polnik, M., additional, Abramczuk-Piekutowska, D., additional, Jurkiewicz, D., additional, Luczak, S., additional, Kowalski, P., additional, Krajewska-Walasek, M., additional, Sheila, C., additional, Lee, S., additional, Foster, C., additional, Manoranjan, B., additional, Pambit, M., additional, Berns, R., additional, Fotovati, A., additional, Venugopal, C., additional, O'Halloran, K., additional, Narendran, A., additional, Hawkins, C., additional, Ramaswamy, V., additional, Taylor, M., additional, Singhal, A., additional, Hukin, J., additional, Rassekh, R., additional, Yip, S., additional, Singh, S., additional, Duhman, C., additional, Dunn, S., additional, Chen, T., additional, Rush, S., additional, Fuji, H., additional, Ishida, Y., additional, Onoe, T., additional, Kanda, T., additional, Kase, Y., additional, Yamashita, H., additional, Murayama, S., additional, Nakasu, Y., additional, Kurimoto, T., additional, Kondo, A., additional, Sakaguchi, S., additional, Fujimura, J., additional, Saito, M., additional, Arakawa, T., additional, Arai, H., additional, Shimizu, T., additional, Jurkiewicz, E., additional, Daszkiewicz, P., additional, Drogosiewicz, M., additional, Hovestadt, V., additional, Buchhalter, I., additional, Jager, N. N., additional, Stuetz, A., additional, Johann, P., additional, Schmidt, C., additional, Ryzhova, M., additional, Landgraf, P., additional, Hasselblatt, M., additional, Schuller, U., additional, Yaspo, M.-L., additional, von Deimling, A., additional, Eils, R., additional, Modi, A., additional, Patel, M., additional, Berk, M., additional, Wang, L.-x., additional, Plautz, G., additional, Camara-Costa, H., additional, Resch, A., additional, Lalande, C., additional, Kieffer, V., additional, Poggi, G., additional, Kennedy, C., additional, Bull, K., additional, Calaminus, G., additional, Grill, J., additional, Doz, F., additional, Rutkowski, S., additional, Massimino, M., additional, Kortmann, R.-D., additional, Lannering, B., additional, Dellatolas, G., additional, Chevignard, M., additional, Solecki, D., additional, McKinnon, P., additional, Olson, J., additional, Hayden, J., additional, Ellison, D., additional, Buss, M., additional, Remke, M., additional, Lee, J., additional, Caspary, T., additional, Castellino, R., additional, Sabel, M., additional, Gustafsson, G., additional, Fleischhack, G., additional, Benesch, M., additional, Navajas, A., additional, Reddingius, R., additional, Delisle, M.-B., additional, Lafon, D., additional, Sevenet, N., additional, Pierron, G., additional, Delattre, O., additional, Ecker, J., additional, Oehme, I., additional, Mazitschek, R., additional, Lodrini, M., additional, Deubzer, H. E., additional, Kulozik, A. E., additional, Witt, O., additional, Milde, T., additional, Patmore, D., additional, Boulos, N., additional, Wright, K., additional, Boop, S., additional, Janicki, T., additional, Burzynski, S., additional, Burzynski, G., additional, Marszalek, A., additional, Triscott, J., additional, Green, M., additional, Rassekh, S. R., additional, Toyota, B., additional, Dunham, C., additional, Dunn, S. E., additional, Liu, K.-W., additional, Pei, Y., additional, Genovesi, L., additional, Ji, P., additional, Davis, M., additional, Ng, C. G., additional, Cho, Y.-J., additional, Jenkins, N., additional, Copeland, N., additional, Wainwright, B., additional, Tang, Y., additional, Schubert, S., additional, Nguyen, B., additional, Masoud, S., additional, Lee, A., additional, Willardson, M., additional, Bandopadhayay, P., additional, Bergthold, G., additional, Atwood, S., additional, Whitson, R., additional, Qi, J., additional, Beroukhim, R., additional, Tang, J., additional, Oro, A., additional, Link, B., additional, Bradner, J., additional, Vallero, S. G., additional, Bertin, D., additional, Basso, M. E., additional, Milanaccio, C., additional, Peretta, P., additional, Cama, A., additional, Mussano, A., additional, Barra, S., additional, Morana, G., additional, Morra, I., additional, Nozza, P., additional, Fagioli, F., additional, Garre, M. L., additional, Darabi, A., additional, Sanden, E., additional, Visse, E., additional, Stahl, N., additional, Siesjo, P., additional, Vaka, D., additional, Vasquez, F., additional, Weir, B., additional, Cowley, G., additional, Keller, C., additional, Hahn, W., additional, Gibbs, I. C., additional, Partap, S., additional, Yeom, K., additional, Martinez, M., additional, Vogel, H., additional, Donaldson, S. S., additional, Fisher, P., additional, Perreault, S., additional, Guerrini-Rousseau, L., additional, Pujet, S., additional, Kieffer-Renaux, V., additional, Raquin, M. A., additional, Varlet, P., additional, Longaud, A., additional, Sainte-Rose, C., additional, Valteau-Couanet, D., additional, Staal, J., additional, Lau, L. S., additional, Zhang, H., additional, Ingram, W. J., additional, Cho, Y. J., additional, Hathout, Y., additional, Brown, K., additional, Rood, B. R., additional, Handler, M., additional, Hankinson, T., additional, Kleinschmidt-Demasters, B. K., additional, Hutter, S., additional, Jones, D. T., additional, Kagawa, N., additional, Hirayama, R., additional, Kijima, N., additional, Chiba, Y., additional, Kinoshita, M., additional, Takano, K., additional, Eino, D., additional, Fukuya, S., additional, Yamamoto, F., additional, Nakanishi, K., additional, Hashimoto, N., additional, Hashii, Y., additional, Hara, J., additional, Yoshimine, T., additional, Wang, J., additional, Guo, C., additional, Yang, Q., additional, Chen, Z., additional, Filipek, I., additional, Swieszkowska, E., additional, Tarasinska, M., additional, Perek, D., additional, Kebudi, R., additional, Koc, B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Wolff, J., additional, Darendeliler, E., additional, Kerl, K., additional, Gronych, J., additional, McGlade, J., additional, Endersby, R., additional, Hii, H., additional, Johns, T., additional, Sastry, J., additional, Murphy, D., additional, Ronghe, M., additional, Cunningham, C., additional, Cowie, F., additional, Jones, R., additional, Calisto, A., additional, Sangra, M., additional, Mathieson, C., additional, Brown, J., additional, Phuakpet, K., additional, Larouche, V., additional, Bartels, U., additional, Ishida, T., additional, Hasegawa, D., additional, Miyata, K., additional, Ochi, S., additional, Saito, A., additional, Kozaki, A., additional, Yanai, T., additional, Kawasaki, K., additional, Yamamoto, K., additional, Kawamura, A., additional, Nagashima, T., additional, Akasaka, Y., additional, Soejima, T., additional, Yoshida, M., additional, Kosaka, Y., additional, von Bueren, A., additional, Goschzik, T., additional, Kortmann, R., additional, von Hoff, K., additional, Friedrich, C., additional, Muehlen, A. z., additional, Warmuth-Metz, M., additional, Soerensen, N., additional, Deinlein, F., additional, Zwiener, I., additional, Faldum, A., additional, Kuehl, J., additional, KRAMER, K., additional, -Taskar, N. P., additional, Zanzonico, P., additional, Humm, J. L., additional, Wolden, S. L., additional, Cheung, N.-K. V., additional, Venkataraman, S., additional, Alimova, I., additional, Harris, P., additional, Birks, D., additional, Balakrishnan, I., additional, Griesinger, A., additional, Foreman, N. K., additional, Vibhakar, R., additional, Margol, A., additional, Robison, N., additional, Gnanachandran, J., additional, Hung, L., additional, Kennedy, R., additional, Vali, M., additional, Dhall, G., additional, Finlay, J., additional, Erdrich-Epstein, A., additional, Krieger, M., additional, Drissi, R., additional, Fouladi, M., additional, Gilles, F., additional, Judkins, A., additional, Sposto, R., additional, Asgharzadeh, S., additional, Peyrl, A., additional, Chocholous, M., additional, Holm, S., additional, Grillner, P., additional, Blomgren, K., additional, Azizi, A., additional, Czech, T., additional, Gustafsson, B., additional, Dieckmann, K., additional, Leiss, U., additional, Slavc, I., additional, Babelyan, S., additional, Dolgopolov, I., additional, Pimenov, R., additional, Mentkevich, G., additional, Gorelishev, S., additional, Laskov, M., additional, von Bueren, A. O., additional, Nowak, J., additional, Kortmann, R. D., additional, Mynarek, M., additional, Muller, K., additional, Gerber, N. U., additional, Ottensmeier, H., additional, Kwiecien, R., additional, Yankelevich, M., additional, Boyarshinov, V., additional, Glekov, I., additional, Ozerov, S., additional, Gorelyshev, S., additional, Popa, A., additional, Subbotina, N., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Bell, R., additional, Martinez, D., additional, Sullivan, L. M., additional, Santi, M., additional, Burger, P. C., additional, Taube, J. M., additional, Drake, C. G., additional, Pardoll, D. M., additional, Lim, M., additional, Li, L., additional, Wang, W.-G., additional, Pu, J.-X., additional, Sun, H.-D., additional, Ruggieri, R., additional, Symons, M. H., additional, Vanan, M. I., additional, Bolin, S., additional, Schumacher, S., additional, Zeid, R., additional, Yu, F., additional, Vue, N., additional, Gibson, W., additional, Paolella, B., additional, Swartling, F. J., additional, Kieran, M. W., additional, Bradner, J. E., additional, Maher, O., additional, Khatua, S., additional, Tarek, N., additional, Zaky, W., additional, Gupta, T., additional, Mohanty, S., additional, Kannan, S., additional, Jalali, R., additional, Kapitza, E., additional, Denkhaus, D., additional, Muhlen, A. z., additional, van Vuurden, D. G., additional, Garami, M., additional, Fangusaro, J., additional, Davidson, T. B., additional, da Costa, M. J. G., additional, Sterba, J., additional, Clifford, S. C., additional, Finlay, J. L., additional, Schmidt, R., additional, Felsberg, J., additional, Skladny, H., additional, Cremer, F., additional, Reifenberger, G., additional, Kunder, R., additional, Sridhar, E., additional, Moiyadi, A. A., additional, Goel, A., additional, Goel, N., additional, Shirsat, N., additional, Othman, R., additional, Storer, L., additional, Kerr, I., additional, Coyle, B., additional, Law, N., additional, Smith, M. L., additional, Greenberg, M., additional, Laughlin, S., additional, Malkin, D., additional, Liu, F., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Nasir, A., additional, Onion, D., additional, Lourdusamy, A., additional, Grabowska, A., additional, Cai, Y., additional, Bradshaw, T., additional, de Medeiros, R. S. S., additional, Beaugrand, A., additional, Soares, S., additional, Epelman, S., additional, Wang, W., additional, Sultan, M., additional, Wechsler-Reya, R. J., additional, Zapatka, M., additional, Radlwimmer, B., additional, Alderete, D., additional, Baroni, L., additional, Lubinieki, F., additional, Auad, F., additional, Gonzalez, M. L., additional, Puya, W., additional, Pacheco, P., additional, Aurtenetxe, O., additional, Gaffar, A., additional, Gros, L., additional, Cruz, O., additional, Calvo, C., additional, Shinojima, N., additional, Nakamura, H., additional, Kuratsu, J.-i., additional, Hanaford, A., additional, Eberhart, C., additional, Archer, T., additional, Tamayo, P., additional, Pomeroy, S., additional, Raabe, E., additional, De Braganca, K., additional, Gilheeney, S., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Dunkel, I., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Shih, D., additional, Wang, X., additional, Faria, C., additional, Raybaud, C., additional, Tabori, U., additional, Rutka, J., additional, Jacobs, S., additional, De Vathaire, F., additional, Diallo, I., additional, Llanas, D., additional, Verez, C., additional, Diop, F., additional, Kahlouche, A., additional, Puget, S., additional, Thompson, E., additional, Prince, E., additional, Amani, V., additional, Sin-Chan, P., additional, Lu, M., additional, Kleinman, C., additional, Spence, T., additional, Picard, D., additional, Ho, K. C., additional, Chan, J., additional, Majewski, J., additional, Jabado, N., additional, Dirks, P., additional, Huang, A., additional, Madden, J. R., additional, Donson, A. M., additional, Mirsky, D. M., additional, Dubuc, A., additional, Mack, S., additional, Gendoo, D., additional, Luu, B., additional, MacDonald, T., additional, Van Meter, T., additional, Croul, S., additional, Laureano, A., additional, Brugmann, W., additional, Denman, C., additional, Singh, H., additional, Huls, H., additional, Moyes, J., additional, Sandberg, D., additional, Silla, L., additional, Cooper, L., additional, and Lee, D., additional

Published
2014
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13. CLINICAL TRIALS

Author

Stapleton, S., primary, Flanary, J., additional, Hamblin, F., additional, Steinbrueck, S., additional, Rodriguez, L., additional, Tuite, G., additional, Carey, C., additional, Storrs, B., additional, Lavey, R., additional, Fangusaro, J., additional, Jakacki, R., additional, Kaste, S., additional, Goldman, S., additional, Pollack, I., additional, Boyett, J., additional, Kun, L., additional, Gururangan, S., additional, Dombi, E., additional, Steinberg, S., additional, Kieran, M., additional, Ullrich, N., additional, Widemann, B., additional, Lulla, R., additional, Reinholdt, N., additional, Newmark, M., additional, Urban, M., additional, Chi, S., additional, Manley, P., additional, Robison, N., additional, Kroon, H.-A., additional, Stancokova, T., additional, Husakova, K., additional, Deak, L., additional, Onar-Thomas, A., additional, Packer, R., additional, Friedman, H., additional, Poussaint, T. Y., additional, Gudrun, F., additional, Tippelt, S., additional, Zimmermann, M., additional, Rutkowski, S., additional, Warmuth-Metz, M., additional, Pietsch, T., additional, Faldum, A., additional, Bode, U., additional, Slavc, I., additional, Peyrl, A., additional, Chocholous, M., additional, Azizi, A., additional, Czech, T., additional, Dieckmann, K., additional, Haberler, C., additional, Macy, M., additional, Cohen, K., additional, MacDonald, T., additional, Smith, A., additional, Etzl, M., additional, Naranderan, A., additional, Gore, L., additional, DiRenzo, J., additional, Trippett, T., additional, Foreman, N., additional, Dunkel, I., additional, Fisher, M. J., additional, Meyer, J., additional, Roberts, T., additional, Belasco, J. B., additional, Phillips, P. C., additional, Lustig, R., additional, Cahill, A. M., additional, Laureano, A., additional, Huls, H., additional, Somanchi, S., additional, Denman, C., additional, Liadi, I., additional, Khatua, S., additional, Varadarajan, N., additional, Champlin, R., additional, Lee, D., additional, Cooper, L., additional, Silla, L., additional, Gopalakrishnan, V., additional, Legault, G., additional, Hagiwara, M., additional, Ballas, M., additional, Brown, K., additional, Vega, E., additional, Nusbaum, A., additional, Bloom, M., additional, Hochman, T., additional, Goldberg, J., additional, Golfinos, J., additional, Roland, J. T., additional, Allen, J., additional, Karajannis, M., additional, Bergner, A., additional, Giovannini, M., additional, Welling, D. B., additional, Niparko, J., additional, Slattery, W., additional, Blakeley, J., additional, Owens, C., additional, Sung, L., additional, Lowis, S., additional, Gentet, J.-C., additional, Bouffet, E., additional, Henry, J., additional, Bala, A., additional, Freeman, S., additional, King, A., additional, Rutherford, S., additional, Mills, S., additional, Huson, S., additional, McBain, C., additional, Lloyd, S., additional, Evans, G., additional, McCabe, M., additional, Lee, Y., additional, Bartels, U., additional, Tabori, U., additional, Jansen, L., additional, Mabbott, D., additional, Huang, A., additional, Aguilera, D., additional, Mazewski, C., additional, McNall, R., additional, Hayes, L., additional, Liu, Y., additional, Castellino, R., additional, Cole, D., additional, Lester-McCully, C., additional, Warren, K., additional, Campigotto, F., additional, Turner, C., additional, Zimmerman, M. A., additional, Chordas, C., additional, Rubin, J., additional, Isakoff, M., additional, Pan, W., additional, Khatib, Z., additional, Comito, M., additional, Bendel, A., additional, Pietrantonio, J., additional, Kondrat, L., additional, Hubbs, S., additional, Neuberg, D., additional, Wetmore, C., additional, Broniscer, A., additional, Wright, K., additional, Armstrong, G., additional, Baker, J., additional, Pai-Panandiker, A., additional, Patay, Z., additional, Ramachandran, A., additional, Turner, D., additional, Gajjar, A., additional, and Stewart, C., additional

Published
2012
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14. Assessing Sleeping Beauty Transpositions for T-Cell Immunotherapy by Supercomputer-Based High-Throughput Profiling of Integration Events

Author

Ang, S.O., primary, Maiti, S.N., additional, Moriarity, B., additional, Andrews, K., additional, Ossowski, M., additional, Tzeng, K., additional, Talbot, R., additional, Kellar, D., additional, Huls, H., additional, Kebriaei, P., additional, Kelly, S., additional, Shpall, E., additional, Largaespada, D.A., additional, Champlin, R., additional, Hackett, P.B., additional, and Cooper, L.J.N., additional

Published
2012
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17. Digital Multiplexed Quantification of Both T-Cell Receptor β-Chain and α-Chain Diversity in T Cells Using the Nanostring nCounter Assay System

Author

Maiti, S.N., primary, Zhang, M., additional, Bernatchez, C., additional, Torikai, H., additional, Kellar, D., additional, Gibbons, H., additional, Hernandez, J., additional, Andersson, H., additional, Huls, H., additional, Lee, D., additional, Hwu, P., additional, Radvanyi, L., additional, and Cooper, L., additional

Published
2011
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19. Genetic Reprogramming and Editing of T Cells Using the Sleeping Beauty System and Designer Zinc Finger Nucleases

Author

Torikai, H., primary, Reik, A., additional, Yuen, C., additional, Zhou, Y., additional, Kellar, D., additional, Huls, H., additional, Warren, E.H., additional, Tykodi, S.S., additional, Gregory, P.D., additional, Holmes, M.C., additional, Rebar, E.J., additional, Lee, D.A., additional, Champlin, R.E., additional, Bonini, C., additional, and Cooper, L.J.N., additional

Published
2011
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21. High Throughput Non-Viral Gene Transfer of T Cells by Micro-Electroporators to Generate CD19-Specific Cells for Immediate Infusion

Author

Choi, Y., primary, Maiti, S., additional, Yuen, C., additional, Huls, H., additional, Biswal, S.L., additional, Raphael, R., additional, Killian, T.C., additional, Stark, D.J., additional, Lee, D.A., additional, Shpall, E.J., additional, Kebriaei, P., additional, Champlin, R.E., additional, and Cooper, L.J.N., additional

Published
2009
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22. PET imaging of T cells derived from umbilical cord blood

Author

Singh, H, primary, Najjar, A M, additional, Olivares, S, additional, Nishii, R, additional, Mukhopadhyay, U, additional, Alauddin, M, additional, Manuri, P R, additional, Huls, H, additional, Lee, D A, additional, Dotti, G, additional, Bollard, C, additional, Simmons, P J, additional, Shpall, E J, additional, Champlin, R E, additional, Gelovani, J G, additional, and Cooper, L J N, additional

Published
2008
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25. The clinical use of donor-derived virus-specific cytotoxic T lymphocytes reactive against cytomegalovirus (CMV), adenovirus, and epstein barr virus (EBV)

Author

Bollard, C.M., Myers, G.D., Leen, A., Huls, H., Buza, E., Chang, J., Leung, K., Carrum, G., Krance, R.A., Molldrem, J., Brenner, M.K., Rooney, C.M., and Heslop, H.E.

Subjects
stomatognathic diseases, Transplantation, otorhinolaryngologic diseases, hemic and immune systems, chemical and pharmacologic phenomena, Hematology
Published
2006
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29. Assessment of on-the-road driving performance in patients with major depressive disorder treated with esketamine nasal spray.

Author

Dijkstra, F., Van De Loo, A., Abdulahad, S., Bosma, E., Hartog, M., Huls, H., Kuijper, D., De Vries, E., Singh, J., Aluisio, L., Zannikos, P., Solanki, B., Stuurman, F., Jacobs, G., and Verster, J.

Subjects
PSYCHOTIC depression, MENTAL depression, DRUNK driving, INTRANASAL medication, BLOOD alcohol, INTRANASAL administration
Abstract

Introduction: Intranasal esketamine administration demonstrates rapid improvement in symptoms of treatment-resistent depression. Transient adverse effects (dissociative symptoms, sedation, dizziness) that could impact driving performance occur routinely in the hours after esketamine administration. Objectives: To investigate effects of 84 mg esketamine on on-theroad driving performance. Methods: Part A used a single-blind, double-dummy, randomized 3-period, cross-over design to compare effects of esketamine vs placebo on next-morning driving. Alcohol (blood alcohol concentration= 0.05%) established assay sensitivity. In Part B, esketamine was administered twice weekly, and weekly driving tests were conducted 6h after administraton. Twenty-seven patients with DSM-5-defined mild-to-moderate major depressive disorder without psychotic features completed a 100-km driving test on a public highway in normal traffic. Primary outcome was Standard Deviation of Lateral Position (SDLP;cm;weaving of car). Part A driving assessments were conducted 18±2 hours postadministration. Part B driving tests were conducted 6±0.5 hours post-treatment. Results: In Part A, alcohol significantly impaired driving performance: Least-square means (95%CI) for delta SDLP (cm) compared with placebo: [SDLP = +1.83 (1.03;2.62)]. There was no significant difference between esketamine and placebo, [SDLP = -0.23 (-1.04;0.58)]. Weekly driving tests showed no significant differences between placebo baseline SDLP and after esketamine administration over 4 weeks (Day 11: [SDLP = -0.96 (-3.72;1.81)], Day 18: [SDLP = -0.56 (-3.33;2.20)], Day 25: [SDLP = -1.05 (-3.82;1.71)]). Conclusions: In MDD patients, esketamine did not significantly impair on-road driving performance the next morning following a single dose, or 6 hours after repeated administrations. These results support the label recommendation to not drive on the day of esketamine dosing. Disclosure: The study and the editorial assistance provided by Ann C Sherwood, PhD were funded by Janssen R&D. [ABSTRACT FROM AUTHOR]

Published
2020

32. Disputatio Iuridica Inauguralis, De Iure Circa Haereticos

Author

Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, Orville, Carl, Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, and Orville, Carl

Abstract

Quam ... In Illustri Hac Academia Viadrina, Praeside Dn. Henrico Cocceio ICto ... Publicae disquisitioni submittit & sistit Carolus d'Orville, Cassellano-Hassus. Ad D. XXIV. Iun. An MDCIC., Nicht identisch mit VD17 14:026259B (Abweichungen u.a. im Erscheinungsvermerk, dort "Literis" statt "Typis"; anderer Zeilenumbruch auf der Titelseite: dort "... Facultatis Juri-||dicae Ordinario ...")., Alternativer Fingerprint für die Variante mit [1] Bl. "Summaria" am Schluß: s,r- i-in 4.i- Chtu 3 1699R, Schlüsselseiten aus dem Exemplar der HAB Wolfenbüttel: Rw 88 (10), Vorlageform des Erscheinungsvermerks: Francofurti ad Viadrum, Typis Christophori Zeitleri

33. Disputatio Iuridica Inauguralis, De Iure Circa Haereticos

Author

Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, Orville, Carl, Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, and Orville, Carl

Abstract

Quam ... In Illustri Hac Academia Viadrina, Praeside Dn. Henrico Cocceio ICto ... Publicae disquisitioni submittit & sistit Carolus d'Orville, Cassellano-Hassus. Ad D. XXIV. Iun. An MDCIC., Nicht identisch mit VD17 14:026259B (Abweichungen u.a. im Erscheinungsvermerk, dort "Literis" statt "Typis"; anderer Zeilenumbruch auf der Titelseite: dort "... Facultatis Juri-||dicae Ordinario ...")., Alternativer Fingerprint für die Variante mit [1] Bl. "Summaria" am Schluß: s,r- i-in 4.i- Chtu 3 1699R, Schlüsselseiten aus dem Exemplar der HAB Wolfenbüttel: Rw 88 (10), Vorlageform des Erscheinungsvermerks: Francofurti ad Viadrum, Typis Christophori Zeitleri

34. Disputatio Iuridica Inauguralis, De Iure Circa Haereticos

Author

Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, Orville, Carl, Huls, H. G., Coccejus, S., Pagenstecher, A. A., Meinertzhagen, Daniel, Schoppachius, J. P., Cocceji, Heinrich, and Orville, Carl

Abstract

Quam ... In Illustri Hac Academia Viadrina, Praeside Dn. Henrico Cocceio ICto ... Publicae disquisitioni submittit & sistit Carolus d'Orville, Cassellano-Hassus. Ad D. XXIV. Iun. An MDCIC., Nicht identisch mit VD17 23:657516W (Abweichungen u.a. im Erscheinungsvermerk, dort "Typis" statt "Literis"; anderer Zeilenumbruch auf der Titelseite: dort "... Facultatis Juridicae|| Ordinario ..."), Schlüsselseiten aus dem Exemplar der SLUB Dresden: Coll.diss.A.21,29, Signaturformel: [1], A - C4, D3, Vorlageform des Erscheinungsvermerks: Francofurti ad Viadrum, Literis Christophori Zeitleri

37. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Author

Dean A. Lee, Helen Huls, Michael C. Holmes, Pei-Qi Liu, Chiara Bonini, Laurence J.N. Cooper, Partow Kebriaei, Yuanyue Zhou, Sourindra Maiti, Richard E. Champlin, Edward J. Rebar, Luigi Naldini, Brian Rabinovitch, Hiroki Torikai, Philip D. Gregory, Ling Zhang, Andreas Reik, Jeffrey C. Miller, Torikai, H1, Reik, A, Liu, Pq, Zhou, Y, Zhang, L, Maiti, S, Huls, H, Miller, Jc, Kebriaei, P, Rabinovitch, B, Lee, Da, Champlin, Re, Bonini, MARIA CHIARA, Naldini, Luigi, Rebar, Ej, Gregory, Pd, Holmes, Mc, and Cooper, Lj

Subjects
Adult, CD3 Complex, T-Lymphocytes, T cell, Antigens, CD19, Immunology, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, Streptamer, Biology, Lymphocyte Activation, Biochemistry, Epitopes, Gene Knockout Techniques, 03 medical and health sciences, 0302 clinical medicine, CD28 Antigens, Antigens, Neoplasm, medicine, Humans, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, Cells, Cultured, 030304 developmental biology, 0303 health sciences, T-cell receptor, Zinc Fingers, Gene Therapy, Cell Biology, Hematology, Endonucleases, Molecular biology, Recombinant Proteins, Chimeric antigen receptor, 3. Good health, Cell biology, medicine.anatomical_structure, Immunotherapy, Genetic Engineering, K562 Cells, CD8, 030215 immunology
Abstract

Clinical-grade T cells are genetically modified ex vivo to express a chimeric antigen receptor (CAR) to redirect specificity to a tumor associated antigen (TAA) thereby conferring antitumor activity in vivo. T cells expressing a CD19-specific CAR recognize B-cell malignancies in multiple recipients independent of major histocompatibility complex (MHC) because the specificity domains are cloned from the variable chains of a CD19 monoclonal antibody. We now report a major step toward eliminating the need to generate patient-specific T cells by generating universal allogeneic TAA-specific T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR+ T cells to eliminate expression of the endogenous αβ T-cell receptor (TCR) to prevent a graft-versus-host response without compromising CAR-dependent effector functions. Genetically modified T cells were generated using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nucleases. We show that these engineered T cells display the expected property of having redirected specificity for CD19 without responding to TCR stimulation. CAR+TCRneg T cells of this type may potentially have efficacy as an off-the-shelf therapy for investigational treatment of B-lineage malignancies.

Published
2012
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40. Frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy.

Author

Kemps S, Soleyman M, Huls H, Labots M, and Crul M

Subjects
Adult, Humans, Infant, Body Weight, Body Surface Area, Lymphoma, Leukemia, Pancreatic Neoplasms
Abstract

Objectives: Most cytostatics used in cancer treatment are dosed on body surface area (BSA). To administer an appropriate dose it is therefore necessary to know the patient's correct body weight. However, evidence is lacking on how often, after initiation of treatment, body weight should be measured to recalculate BSA. We aimed to assess the relevance of weight measurements during chemotherapy treatment., Methods: Over a 2 year period we analysed BSA changes in adult patients undergoing chemotherapy treatment. The frequency of and median time to ≥10% BSA change was determined. We assumed a 10% BSA change required dose adjustment and was therefore clinically relevant., Results: Using a database query, data from 2276 patients were used for descriptive statistics, life table analyses and generalised estimating equations. The frequency of ≥10% BSA change occurred in a maximum of 7.6% of the patients, depending on the tumour type. Descriptive statistics in the indications with more than 100 patients showed that BSA changes of ≥10% occurred after 84 days. The groups with the earliest BSA changes were patients with acute leukaemia, lymphoma and pancreatic cancer., Conclusions: Our observations from real-world data indicate it is safe to omit the current requirement for monthly weight measurements. We advise that during chemotherapy, measuring the body weight in patients who have acute leukaemia, lymphoma or pancreatic cancer or who are under 20 years of age, should be performed at least every 3 months. For other patients, extending this period to a 6-monthly weight measurement should be considered., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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41. Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies.

Author

Singh H, Srour SA, Milton DR, McCarty J, Dai C, Gaballa MR, Ammari M, Olivares S, Huls H, De Groot E, Marin D, Petropoulos D, Olson AL, Anderlini P, Im JS, Khouri I, Hosing CM, Rezvani K, Champlin RE, Shpall EJ, Cooper LJN, and Kebriaei P

Subjects
Humans, Adaptor Proteins, Signal Transducing, Antigens, CD19, B-Lymphocytes, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Receptors, Antigen, T-Cell genetics, Hematologic Neoplasms etiology, Neoplasms drug therapy
Abstract

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity., Competing Interests: The technology was advanced through research conducted at MD Anderson by LC. In January 2015, the technology was licensed by The University of Texas MD Anderson Cancer Center for commercial application to Alaunos Therapeutics formerly Ziopharm Oncology, Inc., and Precigen formerly Intrexon Corporation, in exchange for equity interests in each of these companies. LC and some co-authors received equity because of the licensing of this technology. From 2015 to 2021 LC was Chief Executive Officer at ZIOPHARM. The information being reported in this publication is research in which The University of Texas MD Anderson Cancer Center has an institutional financial conflict of interest. Because The University of Texas MD Anderson Cancer Center is committed to the protection of human subjects and the effective management of its financial conflicts of interest in relation to its research activities, The University of Texas MD Anderson Cancer Center has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to The University of Texas MD Anderson Cancer Center’s conduct of this research. EG and LC were formerly employed by Alaunos Therapeutics and have equity ownership in the company. KR and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical and Affimed GmbH. KR participates on the Scientific Advisory Board for GemoAb, AvengeBio, Virogin Biotech, GSK, Bayer, Navan Technologies, and Caribou Biosciences. ES participates on Scientific Advisory Boards for Adaptimmune, Axio, Navan, Fibroblasts and Fibrobiologics, and the NY Blood Center; has licensing or patents with Takeda and Affimed; and honorarium from Bayer Healthcare Pharmaceuticals. PK has served on advisory boards for Kite and Pfizer; received research support from Amgen and Alaunos; and has been a consultant for Jazz. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Singh, Srour, Milton, McCarty, Dai, Gaballa, Ammari, Olivares, Huls, De Groot, Marin, Petropoulos, Olson, Anderlini, Im, Khouri, Hosing, Rezvani, Champlin, Shpall, Cooper and Kebriaei.)

Published
2022
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42. The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder.

Author

Dijkstra FM, van de Loo AJ, Abdulahad S, Bosma ER, Hartog M, Huls H, Kuijper DC, de Vries E, Solanki B, Singh J, Aluisio L, Zannikos P, Stuurman FE, Jacobs GE, and Verster JC

Subjects
Antidepressive Agents adverse effects, Cross-Over Studies, Double-Blind Method, Humans, Ketamine, Psychomotor Performance, Single-Blind Method, Automobile Driving, Depressive Disorder, Major drug therapy
Abstract

Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance., Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients., Methods: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car)., Results: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p -value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p  < 0.001), whereas esketamine did not: (ΔSDLP = -0.23 (-1.04; 0.58), p  = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = -0.96 (-3.72; 1.81), p  = 0.493), Day 18: (ΔSDLP = -0.56 (-3.33; 2.20), p  = 0.686) and Day 25: (ΔSDLP = -1.05 (-3.82; 1.71), p  = 0.451)., Conclusions: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.

Published
2022
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43. Adoptive immunotherapy with double-bright (CD56 bright /CD16 bright ) expanded natural killer cells in patients with relapsed or refractory acute myeloid leukaemia: a proof-of-concept study.

Author

Silla L, Valim V, Pezzi A, da Silva M, Wilke I, Nobrega J, Vargas A, Amorin B, Correa B, Zambonato B, Scherer F, Merzoni J, Sekine L, Huls H, Cooper LJ, Paz A, and Lee DA

Subjects
Adolescent, Adult, Brazil epidemiology, CD56 Antigen immunology, Child, Female, GPI-Linked Proteins analysis, GPI-Linked Proteins immunology, Graft vs Host Disease etiology, Humans, Immunotherapy, Adoptive adverse effects, Killer Cells, Natural immunology, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute immunology, Male, Middle Aged, Proof of Concept Study, Receptors, IgG immunology, Young Adult, CD56 Antigen analysis, Immunotherapy, Adoptive methods, Killer Cells, Natural transplantation, Leukemia, Myeloid, Acute therapy, Receptors, IgG analysis
Abstract

Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28·7%. Natural killer (NK)-cell have anti-leukaemic activity. Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56 bright /CD16 bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (10 6 -10 7 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Published
2021
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44. Development and Validation of the Immune Status Questionnaire (ISQ).

Author

J F Wilod Versprille L, J A E van de Loo A, Mackus M, Arnoldy L, A L Sulzer T, Vermeulen SA, Abdulahad S, Huls H, Baars T, Scholey A, Kraneveld AD, Garssen J, and Verster JC

Subjects
Adult, Female, Humans, Male, Self-Assessment, Young Adult, Health Status, Immunity, Innate immunology, Surveys and Questionnaires standards
Abstract

The self-assessment of perceived immune status is important, as this subjective observation leads individuals to decide whether or not to seek medical help or adapt their lifestyle. In addition, it can be used in clinical settings and research. The aim of this series of studies was to develop and validate a short questionnaire to assess perceived immune functioning. Five surveys were conducted among Dutch and International young healthy adults (18-30 years old), and two others among older age groups with various health complaints. For the first study, an existing immune functioning scale was modified and elaborated resulting in 23 immune-health-related items, of which the occurrence was rated on a 5-point Likert scale. A student sample was surveyed, and the results were used to shorten the 23-item listing into a 7-item scale with a predictive validity of 85%. Items include "sudden high fever", "diarrhea", "headache", "skin problems (e.g., acne and eczema)", "muscle and joint pain", "common cold" and "coughing". The scale is named Immune Status Questionnaire (ISQ), and it aims to assess perceived immune status over the preceding year. The second study revealed that the ISQ score correlated significantly with a 1-item perceived immune functioning (r = 0.383, p < 0.0001). In the third study, the final Likert scale descriptors were determined ("never", "sometimes", "regularly", "often" and "(almost) always)". The fourth study showed that the test-retest reliability of the ISQ is acceptable (r = 0.80). The fifth study demonstrated the association of ISQ scores with various neuropsychological and health correlates in an international sample, including perceived health and immune fitness, as well as levels of stress, fatigue, depression and anxiety. Study 6 demonstrated significant associations between ISQ scores and experiencing irritable bowel syndrome (IBS) symptoms in a sample of insomnia patients. Study 7 compared the effect of a dietary intervention in participants reporting "poor health" versus "normal health". It is shown that ISQ scores can differentiate between those with poor and normal health, and that an effective intervention is associated with a significant improvement in ISQ scores. Data from Study 7 were further used to determine an ISQ cut-off value for reduced immune functioning, and a direct comparison with 1-item perceived immune functioning scores enabled constructing the final scoring format of the ISQ. In conclusion, the ISQ has appropriate face, content, and construct validity and is a reliable, stable and valid method to assess the past 12 month's perceived immune status.

Published
2019
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45. Inclusion and Exclusion Criteria of Clinical Trials for Insomnia.

Author

Huls H, Abdulahad S, Mackus M, van de Loo AJAE, Roehrs T, Roth T, and Verster JC

Abstract

Randomized controlled trials (RCTs) have eligibility criteria for the inclusion of participants. Ideally, the RCT sample would be representative for the patient population that will use the drug under investigation. However, external validity may be at stake when applying too many or too restrictive eligibility criteria. The current two-part study examined (1) the currently applied eligibility criteria in Phase II and III RCTs examining sleep medication; (2) how these criteria match with the insomnia population as a whole; and (3) how inclusion rates can be changed by an adaptation of these criteria. In the first study, insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility criteria were identified. The second study comprised a survey among self-reported insomnia patients. It was determined to what extent RCT eligibility criteria match the characteristics of this patient population. Of the n = 519 patients that completed the survey only n = 2 (0.4%) met all eligibility criteria of current RCTs. RCT enrolment criteria are not representative for the insomnia patient population as a whole. Being less rigorous in applying upper or lower criteria limits results in a significant increase in the number of eligible patients, and increases the representativeness of RCTs for the insomnia patient population as a whole. The current analysis demonstrates that is important to thoroughly reconsider the use eligibility criteria and their inclusion ranges, and to have a theoretical basis for using them.

Published
2018
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46. Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models.

Author

Crossland DL, Denning WL, Ang S, Olivares S, Mi T, Switzer K, Singh H, Huls H, Gold KS, Glisson BS, Cooper LJ, and Heymach JV

Subjects
Animals, CD56 Antigen genetics, Cell Line, Tumor, Glioma pathology, Humans, Lung Neoplasms pathology, Lymphocyte Activation immunology, Mice, Mice, Inbred NOD, Mice, Nude, Neuroblastoma pathology, Small Cell Lung Carcinoma pathology, Transposases metabolism, Xenograft Model Antitumor Assays, CD56 Antigen metabolism, Glioma therapy, Lung Neoplasms therapy, Neuroblastoma therapy, Receptors, Chimeric Antigen metabolism, Small Cell Lung Carcinoma therapy, T-Lymphocytes immunology, T-Lymphocytes transplantation
Abstract

The CD56 antigen (NCAM-1) is highly expressed on several malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer and neuroblastoma, tumor types for which new therapeutic options are needed. We hypothesized that CD56-specific chimeric antigen receptor (CAR) T cells could target and eliminate CD56-positive malignancies. Sleeping Beauty transposon-generated CD56R-CAR T cells exhibited αβT-cell receptors, released antitumor cytokines upon co-culture with CD56 + tumor targets, demonstrated a lack of fratricide, and expression of cytolytic function in the presence of CD56 + stimulation. The CD56R-CAR + T cells are capable of killing CD56 + neuroblastoma, glioma, and SCLC tumor cells in in vitro co-cultures and when tested against CD56 + human xenograft neuroblastoma models and SCLC models, CD56R-CAR + T cells were able to inhibit tumor growth in vivo. These results indicate that CD56-CARs merit further investigation as a potential treatment for CD56 + malignancies.

Published
2018
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47. Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography.

Author

Najjar AM, Manuri PR, Olivares S, Flores L 2nd, Mi T, Huls H, Shpall EJ, Champlin RE, Turkman N, Paolillo V, Roszik J, Rabinovich B, Lee DA, Alauddin M, Gelovani J, and Cooper LJ

Subjects
Animals, Arabinofuranosyluracil analogs & derivatives, Arabinofuranosyluracil chemistry, Cell Line, Ganciclovir pharmacology, Gene Transfer Techniques, Humans, Luciferases metabolism, Mice, Radiopharmaceuticals chemistry, Transgenes, Xenopus, Herpesvirus 1, Human enzymology, Positron-Emission Tomography methods, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes metabolism, Thymidine Kinase metabolism, Transposases metabolism
Abstract

Purpose: We have incorporated a positron emission tomography (PET) functionality in T cells expressing a CD19-specific chimeric antigen receptor (CAR) to non-invasively monitor the adoptively transferred cells., Procedures: We engineered T cells to express CD19-specific CAR, firefly luciferase (ffLuc), and herpes simplex virus type-1 thymidine kinase (TK) using the non-viral-based Sleeping Beauty (SB) transposon/transposase system adapted for human application. Electroporated primary T cells were propagated on CD19 + artificial antigen-presenting cells., Results: After 4 weeks, 90 % of cultured cells exhibited specific killing of CD19 + targets in vitro, could be ablated by ganciclovir, and were detected in vivo by bioluminescent imaging and PET following injection of 2'-deoxy-2'-[ 18 F]fluoro-5-ethyl-1-β-D-arabinofuranosyl-uracil ([ 18 F]FEAU)., Conclusion: This is the first report demonstrating the use of SB transposition to generate T cells which may be detected using PET laying the foundation for imaging the distribution and trafficking of T cells in patients treated for B cell malignancies., Competing Interests: The technology described in this publication was advanced through research conducted at the University of Texas MD Anderson Cancer Center (MD Anderson) by Laurence Cooper. In January 2015, the technology was licensed by MD Anderson for commercial application to ZIOPHARM Oncology, Inc., and Intrexon Corporation, in exchange for equity interests in each of these companies. Laurence Cooper, Amer M. Najjar, Pallavi R. Manuri, Simon Olivares, Tiejuan Mi, Helen Huls, Richard E. Champlin, Brian Rabinovich, and Dean A. Lee are eligible in accordance with the Rules of Board of Regents of The University of Texas System to share in the proceeds of the disposition of the equity received by MD Anderson as a result of the licensing of this technology. On May 7, 2015, Dr. Cooper was appointed as the Chief Executive Officer at ZIOPHARM. Dr. Cooper is now a Visiting Scientist at MD Anderson where he continues to help supervise the development of this technology. The research being reported in this publication is research in which The University of Texas MD Anderson Cancer Center has an institutional financial conflict of interest. Because MD Anderson is committed to the protection of human subjects and the effective management of its financial conflicts of interest in relation to its research activities, MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to MD Anderson’ s conduct of this research.

Published
2016
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48. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

Author

Hurton LV, Singh H, Najjar AM, Switzer KC, Mi T, Maiti S, Olivares S, Rabinovich B, Huls H, Forget MA, Datar V, Kebriaei P, Lee DA, Champlin RE, and Cooper LJ

Subjects
Animals, Antigens, CD19 metabolism, Humans, Immunotherapy, Adoptive, Lymphocyte Activation, Mice, Precursor Cells, T-Lymphoid physiology, Recombinant Fusion Proteins metabolism, Signal Transduction, Interleukin-15 metabolism, Neoplasms, Experimental therapy, Receptors, Antigen, T-Cell metabolism, T-Lymphocyte Subsets physiology
Abstract

Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (T SCM ) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR + T cells with preserved T SCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19 + leukemia. Long-lived T cells were CD45RO neg CCR7 + CD95 + , phenotypically most similar to T SCM , and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR + T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials., Competing Interests: Some of the technology described was advanced through research conducted at the M. D. Anderson Cancer Center by L.J.N.C. The M. D. Anderson Cancer Center, L.J.N.C., L.V.H., K.C.S., H.S., T.M., S.M., S.O., B.R., M.-A.F., H.H., A.M.N., R.E.C., and D.A.L. all have or had a financial interest in ZIOPHARM Oncology, Inc., and Intrexon Corporation. On May 7, 2015, L.J.N.C. was appointed as the Chief Executive Officer at ZIOPHARM. L.J.N.C. is now a Visiting Scientist at the M. D. Anderson Cancer Center. A patent application based on this manuscript has been filed.

Published
2016
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49. Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

Author

Thokala R, Olivares S, Mi T, Maiti S, Deniger D, Huls H, Torikai H, Singh H, Champlin RE, Laskowski T, McNamara G, and Cooper LJ

Subjects
Animals, B-Lymphocytes immunology, B-Lymphocytes pathology, CD28 Antigens genetics, CD28 Antigens immunology, Caspase 9 genetics, Caspase 9 immunology, Cytotoxicity, Immunologic, Disease Models, Animal, Gene Expression, Hematopoietic Stem Cells immunology, Hematopoietic Stem Cells pathology, Humans, Interleukin-3 Receptor alpha Subunit genetics, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Mice, Mice, Inbred NOD, Mice, SCID, Molecular Targeted Therapy, Plasmids, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Recombinant Fusion Proteins genetics, Single-Domain Antibodies genetics, T-Lymphocytes cytology, T-Lymphocytes immunology, Transfection, Tumor Necrosis Factor Receptor Superfamily, Member 9 genetics, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology, Genetic Engineering methods, Immunotherapy, Adoptive methods, Interleukin-3 Receptor alpha Subunit immunology, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Recombinant Fusion Proteins immunology, T-Lymphocytes transplantation
Abstract

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies., Competing Interests: The technology described in this presentation was licensed by MD Anderson for commercial application to Ziopharm Oncology, Inc., and Intrexon Corporation, in exchange for equity interests in each of these companies. Dr. Cooper and all (excluding Tamara Laskowski) the co-authors were eligible to receive equity as a result of the licensing of this technology. All authors have stock options including patents with Intrexon and Ziopharm. The equity was paid out to each author in the second quarter of 2016 and as a result currently none of the authors have a financial interest in either company except Dr. Cooper who has a continuing financial interest as CEO of Ziopharm. Dr. Cooper also has the following disclosures: Royalties (City of Hope Hospital, Duarte, CA), Intellectual property/patent holder (Sangamo BioSciences), ownership interest in Targazyme, Inc., Intrexon, Ziopharm, Immatics. In relation to this study a patent was filed: UTSC.P1286US.P1. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Published
2016
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50. Redirecting T-Cell Specificity to EGFR Using mRNA to Self-limit Expression of Chimeric Antigen Receptor.

Author

Caruso HG, Torikai H, Zhang L, Maiti S, Dai J, Do KA, Singh H, Huls H, Lee DA, Champlin RE, Heimberger AB, and Cooper LJ

Subjects
Antigens, Neoplasm immunology, Cell Line, Tumor, Cell Proliferation, Coculture Techniques, ErbB Receptors immunology, Genetic Engineering, Glioblastoma immunology, Humans, Immunologic Memory, Lymphocyte Activation, RNA, Messenger genetics, T-Cell Antigen Receptor Specificity, CD8-Positive T-Lymphocytes physiology, Cancer Vaccines immunology, Glioblastoma therapy, Immunotherapy, Adoptive methods, Receptors, Antigen, T-Cell genetics, T-Lymphocyte Subsets physiology
Abstract

Potential for on-target, but off-tissue toxicity limits therapeutic application of genetically modified T cells constitutively expressing chimeric antigen receptors (CARs) from tumor-associated antigens expressed in normal tissue, such as epidermal growth factor receptor (EGFR). Curtailing expression of CAR through modification of T cells by in vitro-transcribed mRNA species is one strategy to mitigate such toxicity. We evaluated expression of an EGFR-specific CAR coded from introduced mRNA in human T cells numerically expanded ex vivo to clinically significant numbers through coculture with activating and propagating cells (AaPC) derived from K562 preloaded with anti-CD3 antibody. The density of AaPC could be adjusted to affect phenotype of T cells such that reduced ratio of AaPC resulted in higher proportion of CD8 and central memory T cells that were more conducive to electrotransfer of mRNA than T cells expanded with high ratios of AaPC. RNA-modified CAR T cells produced less cytokine, but demonstrated similar cytolytic capacity as DNA-modified CAR T cells in response to EGFR-expressing glioblastoma cells. Expression of CAR by mRNA transfer was transient and accelerated by stimulation with cytokine and antigen. Loss of CAR abrogated T-cell function in response to tumor and normal cells expressing EGFR. We describe a clinically applicable method to propagate and modify T cells to transiently express EGFR-specific CAR to target EGFR-expressing tumor cells that may be used to limit on-target, off-tissue toxicity to normal tissue.

Published
2016
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