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1. IDH1 MUTATIONS AS A IMMUNOTHERAPEUTIC TARGET FOR BRAIN TUMORS

Author

Archer, G. E., primary, Reap, E., additional, Norberg, P., additional, Cui, X., additional, Schmittling, R., additional, Herndon, J., additional, Chandramohan, V., additional, Riccione, K., additional, Kuan, C.-T., additional, Yan, H., additional, Bigner, D. D., additional, and Sampson, J. H., additional

Published
2014
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2. IMMUNOTHERAPY/BIOLOGICAL THERAPIES

Author

Campian, J., primary, Gladstone, D., additional, Ambady, P., additional, Ye, X., additional, King, K., additional, Borrello, I., additional, Petrik, S., additional, Golightly, M., additional, Holdhoff, M., additional, Grossman, S., additional, Bhardwaj, R., additional, Chakravadhanula, M., additional, Ozols, V., additional, Georges, J., additional, Carlson, E., additional, Hampton, C., additional, Decker, W., additional, Chiba, Y., additional, Hashimoto, N., additional, Kagawa, N., additional, Hirayama, R., additional, Tsuboi, A., additional, Oji, Y., additional, Oka, Y., additional, Sugiyama, H., additional, Yoshimine, T., additional, Choi, B., additional, Gedeon, P., additional, Herndon, J., additional, Sanchez-Perez, L., additional, Mitchell, D., additional, Bigner, D., additional, Sampson, J., additional, Choi, Y. A., additional, Pandya, H., additional, Gibo, D. M., additional, Debinski, W., additional, Cloughesy, T. F., additional, Liau, L. M., additional, Chiocca, E. A., additional, Jolly, D. J., additional, Robbins, J. M., additional, Ostertag, D., additional, Ibanez, C. E., additional, Gruber, H. E., additional, Kasahara, N., additional, Vogelbaum, M. A., additional, Kesari, S., additional, Mikkelsen, T., additional, Kalkanis, S., additional, Landolfi, J., additional, Bloomfield, S., additional, Foltz, G., additional, Pertschuk, D., additional, Everson, R., additional, Jin, R., additional, Safaee, M., additional, Lisiero, D., additional, Odesa, S., additional, Liau, L., additional, Prins, R., additional, Gholamin, S., additional, Mitra, S. S., additional, Richard, C. E., additional, Achrol, A., additional, Kahn, S. A., additional, Volkmer, A. K., additional, Volkmer, J. P., additional, Willingham, S., additional, Kong, D., additional, Shin, J. J., additional, Monje-Deisseroth, M., additional, Cho, Y.-J., additional, Weissman, I., additional, Cheshier, S. H., additional, Kanemura, Y., additional, Sumida, M., additional, Yoshioka, E., additional, Yamamoto, A., additional, Kanematsu, D., additional, Takada, A., additional, Nonaka, M., additional, Nakajima, S., additional, Goto, S., additional, Kamigaki, T., additional, Takahara, M., additional, Maekawa, R., additional, Shofuda, T., additional, Moriuchi, S., additional, Yamasaki, M., additional, Kebudi, R., additional, Cakir, F. B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Darendeliler, E., additional, Lin, Y., additional, Wang, Y., additional, Qiu, X., additional, Jiang, T., additional, Zhang, G., additional, Wang, J., additional, Okada, H., additional, Butterfield, L., additional, Hamilton, R., additional, Drappatz, J., additional, Engh, J., additional, Amankulor, N., additional, Lively, M., additional, Chan, M., additional, Salazar, A., additional, Potter, D., additional, Shaw, E., additional, Lieberman, F., additional, Choi, Y., additional, Park, J., additional, Phuphanich, S., additional, Wheeler, C., additional, Rudnick, J., additional, Hu, J., additional, Mazer, M., additional, Wang, H., additional, Nuno, M., additional, Guevarra, A., additional, Sanchez, C., additional, Fan, X., additional, Ji, J., additional, Chu, R., additional, Bender, J., additional, Hawkins, E., additional, Black, K., additional, Yu, J., additional, Reap, E., additional, Archer, G., additional, Norberg, P., additional, Schmittling, R., additional, Nair, S., additional, Cui, X., additional, Snyder, D., additional, Chandramohan, V., additional, Kuan, C.-T., additional, Yan, H., additional, Reardon, D., additional, Li, G., additional, Recht, L., additional, Fink, K., additional, Nabors, L., additional, Tran, D., additional, Desjardins, A., additional, Chandramouli, N., additional, Duic, J. P., additional, Groves, M., additional, Clarke, A., additional, Hawthorne, T., additional, Green, J., additional, Yellin, M., additional, Rigakos, G., additional, Spyri, O., additional, Nomikos, P., additional, Stavridi, F., additional, Grossi, I., additional, Theodorakopoulou, I., additional, Assi, A., additional, Kouvatseas, G., additional, Papadopoulou, E., additional, Nasioulas, G., additional, Labropoulos, S., additional, Razis, E., additional, Ravi, A., additional, Tang, D. N., additional, Sharma, P., additional, Sengupta, S., additional, Sampath, P., additional, Soto, H., additional, Erickson, K., additional, Malone, C., additional, Hickey, M., additional, Ha, E., additional, Young, E., additional, Ellingson, B., additional, Kruse, C., additional, Sul, J., additional, Hilf, N., additional, Kutscher, S., additional, Schoor, O., additional, Lindner, J., additional, Reinhardt, C., additional, Kreisl, T., additional, Iwamoto, F., additional, Fine, H., additional, Singh-Jasuja, H., additional, Teijeira, L., additional, Gil-Arnaiz, I., additional, Hernandez-Marin, B., additional, Martinez-Aguillo, M., additional, Sanchez, S. d. l. C., additional, Viudez, A., additional, Hernandez-Garcia, I., additional, Lecumberri, M. J., additional, Grandez, R., additional, de Lascoiti, A. F., additional, Garcia, R. V., additional, Thomas, A., additional, Fisher, J., additional, Baron, U., additional, Olek, S., additional, Rhodes, H., additional, Gui, J., additional, Hampton, T., additional, Tafe, L., additional, Tsongalis, G., additional, Lefferts, J., additional, Wishart, H., additional, Kleen, J., additional, Miller, M., additional, Ernstoff, M., additional, Fadul, C., additional, Vlahovic, G., additional, Peters, K., additional, Ranjan, T., additional, Friedman, A., additional, Friedman, H., additional, Lally-Goss, D., additional, Wainwright, D., additional, Dey, M., additional, Chang, A., additional, Cheng, Y., additional, Han, Y., additional, Lesniak, M., additional, Weller, M., additional, Kaulich, K., additional, Hentschel, B., additional, Felsberg, J., additional, Gramatzki, D., additional, Pietsch, T., additional, Simon, M., additional, Westphal, M., additional, Schackert, G., additional, Tonn, J. C., additional, Loeffler, M., additional, Reifenberger, G., additional, Xu, M., additional, and Patil, C., additional

Published
2013
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3. LAB-EXPERIMENTAL (PRE-CLINICAL) THERAPEUTICS AND PHARMACOLOGY

Author

Yang, F. H., primary, Zhang, B., additional, Zhou, D. J., additional, Bie, L., additional, Tom, M. W., additional, Drummond, D. C., additional, Nicolaides, T., additional, Mueller, S., additional, Banerjee, A., additional, Park, J. W., additional, Prados, M. D., additional, James, D. C., additional, Gupta, N., additional, Hashizume, R., additional, Strohbehn, G. W., additional, Zhou, J., additional, Fu, M., additional, Patel, T. R., additional, Piepmeier, J. M., additional, Saltzman, W. M., additional, Xie, Q., additional, Johnson, J., additional, Bradley, R., additional, Ascierto, M. L., additional, Kang, L., additional, Koeman, J., additional, Marincola, F. M., additional, Briggs, M., additional, Tanner, K., additional, Vande Woude, G. F., additional, Tanaka, S., additional, Klofas, L. K., additional, Wakimoto, H., additional, Borger, D. R., additional, Iafrate, A. J., additional, Batchelor, T. T., additional, Chi, A. S., additional, Madhankumar, A. B., additional, Slagle-Webb, B., additional, Rizk, E., additional, Harbaugh, K., additional, Connor, J. R., additional, Sarkar, G., additional, Curran, G. L., additional, Jenkins, R. B., additional, Kurozumi, K., additional, Ichikawa, T., additional, Onishi, M., additional, Fujii, K., additional, Ishida, J., additional, Shimazu, Y., additional, Date, I., additional, Ebsworth, K., additional, Walters, M. J., additional, Ertl, L. S., additional, Wang, Y., additional, Berahovich, R. D., additional, Zhang, P., additional, Powers, J. P., additional, Liu, S.-C., additional, Al Omran, R., additional, Sullivan, T. J., additional, Jaen, J. C., additional, Brown, M., additional, Schall, T. J., additional, Yusuke, N., additional, Shimizu, S., additional, Shishido-Hara, Y., additional, Shiokawa, Y., additional, Nagane, M., additional, Wang, J., additional, Sai, K., additional, Chen, F.-R., additional, Chen, Z.-P., additional, Shi, Z., additional, Zhang, J., additional, Zhang, K., additional, Han, L., additional, Chen, L., additional, Qian, X., additional, Zhang, A., additional, Wang, G., additional, Jia, Z., additional, Pu, P., additional, Kang, C., additional, Kong, L.-Y., additional, Doucette, T. A., additional, Ferguson, S. D., additional, Hachem, J., additional, Yang, Y., additional, Wei, J., additional, Priebe, W., additional, Fuller, G. N., additional, Qiao, W., additional, Rao, G., additional, Heimberger, A. B., additional, Chen, P.-Y., additional, Ozawa, T., additional, Drummond, D., additional, Santos, R., additional, Torre, J. D., additional, Ng, C., additional, Lepe, E. L., additional, Butowski, N., additional, Prados, M., additional, Bankiewicz, K., additional, James, C. D., additional, Cheng, Z., additional, Gong, Y., additional, Ma, Y., additional, Muller-Knapp, S., additional, Knapp, S., additional, Antonio Chiocca, E., additional, Kaur, B., additional, Yu, J. S., additional, Judkowski, V., additional, Bunying, A., additional, Ji, J., additional, Li, Z., additional, Bender, J., additional, Pinilla, C., additional, Srinivasan, V., additional, Dombovy-Johnson, M., additional, Carson-Walter, E., additional, Walter, K., additional, Xu, Z., additional, Popp, B., additional, Schlesinger, D., additional, Gray, L., additional, Sheehan, J., additional, Keir, S. T., additional, Friedman, H. S., additional, Bigner, D. D., additional, Kut, C., additional, Tyler, B., additional, McVeigh, E., additional, Li, X., additional, Herzka, D., additional, Grossman, S., additional, Lasky, J. L., additional, Panosyan, E., additional, Meisen, W. H., additional, Hardcastle, J., additional, Wojton, J., additional, Wohleb, E., additional, Alvarez-Breckenridge, C., additional, Nowicki, M., additional, Godbout, J., additional, Lee, S. Y., additional, Sheehan, J. M., additional, Yin, S., additional, Kaluz, S., additional, Devi, S. N., additional, de Noronha, R., additional, Nicolaou, K. C., additional, Van Meir, E. G., additional, Lachowicz, J. E., additional, Demeule, M., additional, Che, C., additional, Tripathy, S., additional, Jarvis, S., additional, Currie, J.-C., additional, Regina, A., additional, Nguyen, T., additional, Castaigne, J.-P., additional, Zielinska-Chomej, K., additional, Mohanty, C., additional, Viktorsson, K., additional, Lewensohn, R., additional, Driscoll, J. J., additional, Alsidawi, S., additional, Warnick, R. E., additional, Rixe, O., additional, deCarvalho, A. C., additional, Irtenkauf, S., additional, Hasselbach, L., additional, Xin, H., additional, Mikkelsen, T., additional, Sherman, J. H., additional, Siu, A., additional, Volotskova, O., additional, Keidar, M., additional, Gibo, D. M., additional, Dickinson, P., additional, Robertson, J., additional, Rossmeisl, J., additional, Debinski, W., additional, Nair, S., additional, Schmittling, R., additional, Boczkowski, D., additional, Archer, G., additional, Sampson, J. H., additional, Mitchell, D. A., additional, Miller, I. S., additional, Didier, S., additional, Murray, D. W., additional, Issaivanan, M., additional, Coniglio, S. J., additional, Segall, J. E., additional, Al-Abed, Y., additional, Symons, M., additional, Fotovati, A., additional, Hu, K., additional, Triscott, J., additional, Bacha, J., additional, Brown, D. M., additional, Dunn, S. E., additional, Daniels, D. J., additional, Peterson, T. E., additional, Dietz, A. B., additional, Knutson, G. J., additional, Parney, I. F., additional, Diaz, R. J., additional, Golbourn, B., additional, Picard, D., additional, Smith, C., additional, Huang, A., additional, Rutka, J., additional, Saito, N., additional, Fu, J., additional, Yao, J., additional, Wang, S., additional, Koul, D., additional, Yung, W. K. A., additional, Yuan, Y., additional, Sulman, E. P., additional, Colman, H., additional, Lang, F. F., additional, Slat, E. A., additional, Herzog, E. D., additional, Rubin, J. B., additional, Carminucci, A. S., additional, Amendolara, B., additional, Leung, R., additional, Lei, L., additional, Canoll, P., additional, Bruce, J. N., additional, Wojton, J. A., additional, Chu, Z., additional, Kwon, C.-H., additional, Chow, L. M., additional, Palascak, M., additional, Franco, R., additional, Bourdeau, T., additional, Thornton, S., additional, Qi, X., additional, Kitange, G. J., additional, Mladek, A. C., additional, Su, D., additional, Carlson, B. L., additional, Schroeder, M. A., additional, Pokorny, J. L., additional, Bakken, K. K., additional, Gupta, S. K., additional, Decker, P. A., additional, Wu, W., additional, Sarkaria, J. N., additional, Oddou, M. P., additional, Mollard, A., additional, Call, L. T., additional, Vakayalapati, H., additional, Warner, S. L., additional, Sharma, S., additional, Bearss, D. J., additional, Chen, T. C., additional, Cho, H., additional, Wang, W., additional, Hofman, F. M., additional, Flores, C. T., additional, Snyder, D., additional, Sanchez-Perez, L., additional, Pham, C., additional, Friedman, H., additional, Woolf, E., additional, Abdelwahab, M. G., additional, Turner, G., additional, Preul, M. C., additional, Lynch, A., additional, Rho, J. M., additional, Scheck, A. C., additional, Salphati, L., additional, Heffron, T. P., additional, Alicke, B., additional, Barck, K., additional, Carano, R. A., additional, Cheong, J., additional, Greve, J., additional, Lee, L. B., additional, Nishimura, M., additional, Pang, J., additional, Plise, E. G., additional, Reslan, H. B., additional, Zhang, X., additional, GOuld, S. G., additional, Olivero, A. G., additional, Phillips, H. S., additional, Zadeh, G., additional, Jalali, S., additional, Voce, D., additional, Wei, Z., additional, Shijun, K., additional, Nikolai, K., additional, Josh, W., additional, Clayton, C., additional, Bakhtiar, Y., additional, Alkins, R., additional, Burgess, A., additional, Ganguly, M., additional, Wels, W., additional, Hynynen, K., additional, Li, Y. M., additional, Jun, H., additional, Daniel, V., additional, Walter, H. A., additional, Nakashima, H., additional, Nguyen, T. T., additional, Shalkh, I., additional, Goins, W. F., additional, Chiocca, E. A., additional, Pyko, I. V., additional, Nakada, M., additional, Furuyama, N., additional, Lei, T., additional, Hayashi, Y., additional, Kawakami, K., additional, Minamoto, T., additional, Fedulau, A. S., additional, and Hamada, J.-i., additional

Published
2012
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4. LAB-IMMUNOLOGY RESEARCH

Author

Fujita, M., primary, Zhang, R., additional, Nakata, S., additional, Kuzushima, K., additional, Wainwright, D. A., additional, Balyasnikova, I. V., additional, Auffinger, B., additional, Ahmed, A. U., additional, Han, Y., additional, Lesniak, M. S., additional, Knight, A., additional, Arnouk, H., additional, Gillespie, G. Y., additional, Britt, W., additional, Su, Y., additional, Lowdell, M. W., additional, Lamb, L. S., additional, Wang, J., additional, Leiss, L., additional, Choi, B. D., additional, Kuan, C.-T., additional, Cai, M., additional, Bigner, D. D., additional, Sampson, J. H., additional, Shibahara, I., additional, Saito, R., additional, Kanamori, M., additional, Sonoda, Y., additional, Kumabe, T., additional, Kikuchi, T., additional, So, T., additional, Ishii, N., additional, Tominaga, T., additional, Zhang, L., additional, Wang, H., additional, Zhang, I., additional, Chen, X., additional, Da Fonseca, A., additional, Fan, H., additional, Badie, B., additional, Sayour, E. J., additional, McLendon, P., additional, Reynolds, R., additional, McLendon, R., additional, Mitchell, D. A., additional, Sanchez-Perez, L., additional, Pham, C., additional, Snyder, D., additional, Xie, W., additional, Cui, X., additional, McConnell, M. J., additional, Broadley, K. W., additional, Farrand, K., additional, Authier, A., additional, Brown, J. H., additional, Hunn, M., additional, Hermans, I., additional, Cantini, G., additional, Pisati, F., additional, Pessina, S., additional, Finocchiaro, G., additional, Pellegatta, S., additional, Yeung, J. T., additional, Hamilton, R., additional, Pollack, I., additional, Jakacki, R., additional, Okada, H., additional, Choi, B., additional, Schmittling, R. J., additional, Flores, C., additional, Johnson, L., additional, Archer, G. A., additional, Raychaudhuri, B., additional, Rayman, P., additional, Huang, P., additional, Ireland, J., additional, Donnola, S., additional, Hamburdzumyan, D., additional, Finke, J., additional, Vogelbaum, M. A., additional, Batich, K., additional, Reap, E., additional, Archer, G., additional, Sampson, J., additional, Mitchell, D., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Cohen, K. J., additional, Pardoll, D. M., additional, Drake, C. G., additional, Lim, M., additional, Rutledge, W. C., additional, Kong, J., additional, Gao, J., additional, Gutman, D. A., additional, Cooper, L. A., additional, Chisolm, C., additional, Scarpace, L., additional, Mikkelsen, T., additional, Saltz, J. H., additional, Moreno, C. S., additional, Brat, D. J., additional, Everson, R. G., additional, Lisiero, D. N., additional, Soto, H., additional, Liau, L. M., additional, Prins, R. M., additional, Gonzalez, G. C., additional, Chae, M., additional, Peterson, T. E., additional, Parney, I. F., additional, and Johnson, A. J., additional

Published
2012
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5. CLIN-IMMUNOTHERAPY/BIOLOGIC THERAPIES

Author

Pollack, I. F., primary, Jakacki, R. I., additional, Butterfield, L., additional, Okada, H., additional, Chiba, Y., additional, Hashimoto, N., additional, Kagawa, N., additional, Kinoshita, M., additional, Kijima, N., additional, Hirayama, R., additional, Oji, Y., additional, Tsuboi, A., additional, Oka, Y., additional, Sugiyama, H., additional, Yoshimine, T., additional, Valle, R. D., additional, Tejada, S., additional, Inoges, S., additional, Idoate, M. A., additional, de Cerio, A. L. D., additional, Espinos, J., additional, Aristu, J., additional, Gallego, J., additional, Calvo, J. P., additional, Bendandi, M., additional, Zhu, J., additional, Chen, C., additional, Ravelo, A., additional, Yu, E., additional, Dhanda, R., additional, Schnadig, I. D., additional, Zhang, L., additional, Fan, H., additional, Zhang, I., additional, Chen, X., additional, Wang, H., additional, Da Fonseca, A., additional, Badie, B., additional, Butterfield, L. H., additional, Hamilton, R. L., additional, Mintz, A. H., additional, Engh, J. A., additional, Drappatz, J., additional, Lively, M. O., additional, Chan, M. D., additional, Salazar, A. M., additional, Potter, D. M., additional, Shaw, E. G., additional, Lieberman, F. S., additional, Wei, J., additional, Kong, L.-Y., additional, Wang, F., additional, Xu, S., additional, Doucette, T. A., additional, Ferguson, S. D., additional, Yang, Y., additional, McEnery, K., additional, Jethwa, K., additional, Gjyshi, O., additional, Qiao, W., additional, Lang, F. F., additional, Rao, G., additional, Fuller, G. N., additional, Calin, G. A., additional, Heimberger, A. B., additional, Yang, S., additional, Archer, G. E., additional, Miao, H., additional, Cui, X., additional, Xie, W., additional, Snyder, D., additional, Pretorian, A. J., additional, Dechkovskaia, A., additional, Reap, E., additional, Perez, L. A. S., additional, Norberg, P., additional, Schmittling, R., additional, Mitchell, D. A., additional, Sampson, J. H., additional, Lang, F., additional, Calin, G., additional, Walker, D. G., additional, Crough, T., additional, Beagley, L., additional, Smith, C., additional, Jones, L., additional, Khanna, R., additional, Kanemura, Y., additional, Sumida, M., additional, Yoshioka, E., additional, Yamamoto, A., additional, Kanematsu, D., additional, Matsumoto, Y., additional, Fukusumi, H., additional, Takada, A., additional, Nonaka, M., additional, Nakajima, S., additional, Mori, K., additional, Goto, S., additional, Kamigaki, T., additional, Maekawa, R., additional, Shofuda, T., additional, Moriuchi, S., additional, Yamasaki, M., additional, Yeung, J. T., additional, Hamilton, R., additional, Jakacki, R., additional, Pollack, I., additional, Pellegatta, S., additional, Eoli, M., additional, Antozzi, C., additional, Frigerio, S., additional, Bruzzone, M. G., additional, Cuppini, L., additional, Nava, S., additional, Anghileri, E., additional, Cantini, G., additional, Prodi, E., additional, Ciusani, E., additional, Ferroli, P., additional, Saini, M., additional, Broggi, G., additional, Mantegazza, R., additional, Parati, E. A., additional, Finocchiaro, G., additional, Hegde, M., additional, Corder, A., additional, Chow, K. K., additional, Mukherjee, M., additional, Brawley, V. S., additional, Heslop, H. E., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Gibo, D. M., additional, Debinski, W., additional, Bonomo, J., additional, Rossmeisl, J., additional, Robertson, J., additional, Dickinson, P., additional, Salacz, M. E., additional, Camarata, P. J., additional, Ots, M., additional, McIntire, J., additional, Lovick, D., additional, Archer, G., additional, Bigner, D., additional, Friedman, H., additional, Lally-Goss, D., additional, Perry, B., additional, Herndon, J., additional, McGehee, S., additional, McLendon, R., additional, Coleman, R. E., additional, Sampson, J., additional, Grada, Z., additional, Byrd, T., additional, Shaffer, D. R., additional, Ghazi, A., additional, Schonfeld, K., additional, Dotti, G., additional, Heslop, H., additional, Wels, W., additional, Baker, M. L., additional, Robbins, J. M., additional, Dickinson, P. J., additional, York, D., additional, Sturges, B. K., additional, Martin, B., additional, Higgins, R. J., additional, Bringas, J., additional, Bankiewicz, K., additional, Gruber, H. E., additional, Jolly, D. J., additional, Narayana, A., additional, Mathew, M., additional, Kannan, R., additional, Madden, K., additional, Golfinos, J., additional, Parker, E., additional, Ott, P., additional, Pavlick, A., additional, Bota, D. A., additional, Pretto, C., additional, Hantos, P., additional, Hofman, F. M., additional, Chen, T. C., additional, Carrillo, J. A., additional, Schijns, V. E., additional, Stathopoulos, A. A., additional, Prins, R. M., additional, Everson, R., additional, Soto, H., additional, Lisiero, D. N., additional, Young, E., additional, Liau, L. M., additional, Friedman, A., additional, Bigner, D. D., additional, Boczkowski, D., additional, Gururangan, S. G., additional, Grant, G., additional, Driscoll, T., additional, King, J., additional, Nair, S., additional, Fuchs, H., additional, Kurtzberg, J., additional, Shevtsov, M. A., additional, Pozdnyakov, A. V., additional, Kim, A. V., additional, Samochernych, K. A., additional, Guzhova, I. V., additional, Romanova, I. V., additional, Margulis, B. A., additional, and Khachatryan, W. A., additional

Published
2012
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6. IMMUNOTHERAPY

Author

Hickey, M. J., primary, Malone, C. K., additional, Erickson, K. L., additional, Gerschenson, L. E., additional, Lin, A. H., additional, Inagaki, A., additional, Hiraoka, K., additional, Kasahara, N., additional, Mueller, B., additional, Kruse, C. A., additional, Kong, S., additional, Tyler, B., additional, Zhou, J., additional, Carter, B. S., additional, Brem, H., additional, Junghans, R. P., additional, Sampath, P., additional, Lai, R. K., additional, Recht, L. D., additional, Reardon, D. A., additional, Paleologos, N., additional, Groves, M., additional, Rosenfeld, M. R., additional, Davis, T., additional, Green, J., additional, Heimberger, A., additional, Sampson, J., additional, Hashimoto, N., additional, Tsuboi, A., additional, Chiba, Y., additional, Kijima, N., additional, Oka, Y., additional, Kinoshita, M., additional, Kagawa, N., additional, Fujimoto, Y., additional, Sugiyama, H., additional, Yoshimine, T., additional, Birks, S. M., additional, Burnet, M., additional, Pilkington, G. J., additional, Yu, J. S., additional, Wheeler, C. J., additional, Rudnick, J., additional, Mazer, M., additional, Wang, H. Q., additional, Nuno, M. A., additional, Richardson, J. E., additional, Fan, X., additional, Ji, J., additional, Chu, R. M., additional, Bender, J. G., additional, Hawkins, E. W., additional, Black, K. L., additional, Phuphanich, S., additional, Pollack, I. F., additional, Jakacki, R. I., additional, Butterfield, L. H., additional, Okada, H., additional, Hunt, M. A., additional, Pluhar, G. E., additional, Andersen, B. M., additional, Gallardo, J. L., additional, Seiler, C. O., additional, SantaCruz, K. S., additional, Ohlfest, J. R., additional, Bauer, D. F., additional, Lamb, L. S., additional, Harmon, D. K., additional, Zheng, X., additional, Romeo, A. K., additional, Gillespie, G. Y., additional, Parker, J. N., additional, Markert, J. M., additional, Jacobs, V. L., additional, Landry, R. P., additional, De Leo, J. A., additional, Bromberg, J. E., additional, Doorduijn, J., additional, Baars, J. W., additional, van Imhoff, G. W., additional, Enting, R., additional, van den Bent, M. J., additional, Murphy, K. A., additional, Bedi, J., additional, Epstein, A., additional, Olin, M., additional, Andersen, B., additional, Swier, L., additional, Ohlfest, J., additional, Litterman, A. J., additional, Zellmer, D. M., additional, Chiocca, E. A., additional, Aguilar, L. K., additional, Aguilar-Cordova, E., additional, Manzanera, A. G., additional, Harney, K. R., additional, Portnow, J., additional, Badie, B., additional, Lesniak, M., additional, Bell, S., additional, Ray-Chaudhuri, A., additional, Kaur, B., additional, Hardcastle, J., additional, Cavaliere, R., additional, McGregor, J., additional, Lo, S., additional, Chakarvarti, A., additional, Grecula, J., additional, Newton, H., additional, Trask, T. W., additional, Baskin, D. S., additional, New, P. Z., additional, Zeng, J., additional, See, A. P., additional, Phallen, J., additional, Belcaid, Z., additional, Durham, N., additional, Meyer, C., additional, Albesiano, E., additional, Pradilla, G., additional, Ford, E., additional, Hammers, H., additional, Tran, P. T., additional, Pardoll, D., additional, Drake, C. G., additional, Lim, M., additional, Ghazi, A., additional, Ashoori, A., additional, Hanley, P., additional, Salsman, V., additional, Schaffer, D. R., additional, Grada, Z., additional, Kew, Y., additional, Powell, S. Z., additional, Grossman, R., additional, Scheurer, M. E., additional, Leen, A. M., additional, Rooney, C. M., additional, Bollard, C. M., additional, Heslop, H. E., additional, Gottschalk, S., additional, Ahmed, N., additional, Hu, J., additional, Patil, C., additional, Nuno, M., additional, Wheeler, C., additional, Chu, R., additional, Black, K., additional, Yu, J., additional, Marabelle, A., additional, Kohrt, H., additional, Brody, J., additional, Luong, R., additional, Tse, V., additional, Levy, R., additional, Li, Y. M., additional, Jun, H., additional, Shahryar, M., additional, Daniel, V. A., additional, Walter, H. A., additional, Thaipisuttikul, I., additional, Avila, E., additional, Mitchell, D. A., additional, Archer, G. E., additional, Friedman, H. S., additional, Herndon, J. E., additional, Bigner, D. D., additional, Sampson, J. H., additional, Johnson, L. A., additional, Nair, S. K., additional, Schmittling, R., additional, Reap, E., additional, Knisely, J. P., additional, Kluger, H., additional, Flanigan, J., additional, Sznol, M., additional, Yu, J. B., additional, Chiang, V. L., additional, Prins, R. M., additional, Kim, W., additional, Soto, H., additional, Lisiero, D. N., additional, and Liau, L. M., additional

Published
2011
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7. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma

Author

Sampson, J. H., primary, Aldape, K. D., additional, Archer, G. E., additional, Coan, A., additional, Desjardins, A., additional, Friedman, A. H., additional, Friedman, H. S., additional, Gilbert, M. R., additional, Herndon, J. E., additional, McLendon, R. E., additional, Mitchell, D. A., additional, Reardon, D. A., additional, Sawaya, R., additional, Schmittling, R., additional, Shi, W., additional, Vredenburgh, J. J., additional, Bigner, D. D., additional, and Heimberger, A. B., additional

Published
2010
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12. A simple and enzyme-free method for processing infiltrating lymphocytes from small mouse tumors for ELISpot analysis.

Author

Swartz AM, Reap E, Norberg P, Schmittling R, Janetzki S, Sanchez-Perez L, and Sampson JH

Subjects
Animals, Enzymes, Mice, Mice, Inbred C57BL, Cell Separation methods, Enzyme-Linked Immunospot Assay, Lymphocytes, Tumor-Infiltrating cytology, Neoplasms immunology, T-Lymphocytes cytology
Abstract

The ELISpot assay prevails as one of the most sensitive and meaningful assays for the detection of antigen-specific, effector immune responses. Acquisition of cellular analyte for ELISpot analysis is typically not problematic when derived from tissues enriched in lymphocytes (e.g., lymphoid organs and blood); however, cell processing becomes more difficult when lymphocytes represent only a very minor population relative to the source tissue, especially when the source tissue is in limited supply (e.g., small mouse tumors). Traditional enzymatic-based methods for dissociating tumors often result in poor yields, inconsistent lymphocyte enrichment, and can have deleterious effects on lymphocyte phenotype and function. To address these limitations, we have developed an enzyme-free protocol for processing tumor infiltrating lymphocytes (TILs) from small mouse tumors, which enables the enumeration of antigen-specific effector lymphocytes using ELISpot analysis. This procedure is predicated on the dissociation of tumor tissue using gentle agitation with a paddle blender followed by a brief in vitro culture period to remove adherent cells, as well as to revive lymphocytes from a non-responsive state. Although this method is demonstrated with mouse intracerebral tumors, we have found that this protocol is applicable to peripheral tumors and may likely extend to alternative tissue sources wherein lymphocytes exist in low numbers., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2018
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13. Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11).

Author

Gururangan S, Reap E, Schmittling R, Kocak M, Reynolds R, Grant G, Onar-Thomas A, Baxter P, Pollack IF, Phillips P, Boyett J, Fouladi M, and Mitchell D

Subjects
Adolescent, Adult, Cerebellar Neoplasms blood, Chemoradiotherapy, Child, Child, Preschool, Craniotomy, Female, Humans, Male, Medulloblastoma blood, Young Adult, Cerebellar Neoplasms immunology, Cerebellar Neoplasms therapy, Medulloblastoma immunology, Medulloblastoma therapy, T-Lymphocytes, Regulatory immunology
Abstract

Background: We evaluated circulating levels of immunosuppressive regulatory T cells (T regs ) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population., Methods: Eligibility criteria for this biologic study included age 4-21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy., Results: A total of 54 subjects were enrolled on the study [22-CM, 18-MBL, and 14-PFT]. Absolute number and percentage T regs (defined as CD4 + CD25 + FoxP3 + CD127 low/- ) at baseline were decreased in MBL and PFT compared to CM [p = 0.0016 and 0.001, respectively). Patients with MBL and PFT had significantly reduced overall CD4 + T cell count (p = 0.0014 and 0.0054, respectively) compared to those with CM. Radiation and chemotherapy treatment in patients with MBL reduced overall lymphocyte counts; however, within the CD4 + T cell compartment, T regs increased during treatment but gradually declined post therapy., Conclusions: Our results demonstrate that patients with MBL and PFT exhibit overall reduced CD4 + T cell counts at diagnosis but not an elevated proportion of T regs . Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive T regs over time.

Published
2017
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14. Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.

Author

Nair SK, Driscoll T, Boczkowski D, Schmittling R, Reynolds R, Johnson LA, Grant G, Fuchs H, Bigner DD, Sampson JH, Gururangan S, and Mitchell DA

Subjects
Antigens, CD metabolism, Brain Neoplasms drug therapy, Cell Separation, Child, Coculture Techniques, Cytotoxicity Tests, Immunologic, Dendritic Cells drug effects, Dendritic Cells pathology, Flow Cytometry, Granulocyte Colony-Stimulating Factor pharmacology, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Humans, Inhibitor of Apoptosis Proteins genetics, Inhibitor of Apoptosis Proteins metabolism, Medulloblastoma drug therapy, Monocytes cytology, Monocytes drug effects, Monocytes physiology, Peptide Fragments genetics, Peptide Fragments metabolism, Phosphoproteins genetics, Phosphoproteins metabolism, Survivin, Transduction, Genetic, Viral Matrix Proteins genetics, Viral Matrix Proteins metabolism, Brain Neoplasms pathology, Dendritic Cells physiology, Induction Chemotherapy, Leukapheresis, Medulloblastoma pathology
Abstract

Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies on DC phenotype and function. We investigated the ability to generate DCs using cells harvested from pediatric patients with medulloblastoma for potential evaluation of DC-RNA based vaccination approach in this patient population. Cells harvested from medulloblastoma patient leukapheresis following induction chemotherapy and granulocyte colony stimulating factor mobilization were cryopreserved prior to use in DC generation. DCs were generated from the adherent CD14+ monocytes using standard procedures and analyzed for cell recovery, phenotype and function. To summarize, 4 out of 5 patients (80%) had sufficient monocyte recovery to permit DC generation, and we were able to generate DCs from 3 out of these 4 patient samples (75%). Overall, we successfully generated DCs that met phenotypic requisites for DC-based cancer therapy from 3 out of 5 (60%) patient samples and met both phenotypic and functional requisites from 2 out of 5 (40%) patient samples. This study highlights the potential to generate functional DCs for further clinical treatments from refractory patients that have been heavily pretreated with myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the effect of the currently employed standard-of-care therapies on the ex vivo generation of DCs for DC-based clinical studies in cancer patients.

Published
2015
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15. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.

Author

Mitchell DA, Sayour EJ, Reap E, Schmittling R, DeLeon G, Norberg P, Desjardins A, Friedman AH, Friedman HS, Archer G, and Sampson JH

Subjects
Autoantibodies biosynthesis, Cancer Vaccines therapeutic use, Combined Modality Therapy, Dacarbazine adverse effects, Dendritic Cells immunology, Glioblastoma immunology, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Humans, Male, Middle Aged, Temozolomide, Antineoplastic Agents, Alkylating adverse effects, Cancer Vaccines adverse effects, Dacarbazine analogs & derivatives, Dendritic Cells transplantation, Glioblastoma therapy, Granulocyte-Macrophage Colony-Stimulating Factor adverse effects
Abstract

Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (grade 3) immunologic reaction in a patient with newly diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide. Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic workup of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti-GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of temozolomide, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant dose-intensified temozolomide., (©2014 American Association for Cancer Research.)

Published
2015
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16. Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.

Author

Nair SK, De Leon G, Boczkowski D, Schmittling R, Xie W, Staats J, Liu R, Johnson LA, Weinhold K, Archer GE, Sampson JH, and Mitchell DA

Subjects
Blotting, Western, Cells, Cultured, Coculture Techniques, Cytokines immunology, Cytokines metabolism, Cytomegalovirus immunology, Cytomegalovirus metabolism, Cytomegalovirus physiology, Cytotoxicity Tests, Immunologic methods, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Flow Cytometry, Glioblastoma immunology, Glioblastoma pathology, Glioblastoma virology, Humans, Lymphocyte Activation immunology, Male, Middle Aged, Phosphoproteins genetics, Phosphoproteins metabolism, RNA, Viral genetics, RNA, Viral immunology, T-Lymphocytes immunology, Tumor Cells, Cultured, Viral Matrix Proteins genetics, Viral Matrix Proteins metabolism, Young Adult, Cytotoxicity, Immunologic immunology, Phosphoproteins immunology, T-Lymphocytes, Cytotoxic immunology, Viral Matrix Proteins immunology
Abstract

Purpose: Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cytomegalovirus (CMV) antigens in GBM presents a unique opportunity to target these viral proteins for tumor immunotherapy. Although the presence of CMV within malignant gliomas has been confirmed by several laboratories, its relevance as an immunologic target in GBM has yet to be established. The objective of this study was to explore whether T cells stimulated by CMV pp65 RNA-transfected dendritic cells (DC) target and eliminate autologous GBM tumor cells in an antigen-specific manner., Experimental Design: T cells from patients with GBM were stimulated with autologous DCs pulsed with CMV pp65 RNA, and the function of the effector CMV pp65-specific T cells was measured., Results: In this study, we demonstrate the ability to elicit CMV pp65-specific immune responses in vitro using RNA-pulsed autologous DCs generated from patients with newly diagnosed GBM. Importantly, CMV pp65-specific T cells lyse autologous, primary GBM tumor cells in an antigen-specific manner. Moreover, T cells expanded in vitro using DCs pulsed with total tumor RNA demonstrated a 10- to 20-fold expansion of CMV pp65-specific T cells as assessed by tetramer analysis and recognition and killing of CMV pp65-expressing target cells., Conclusion: These data collectively demonstrate that CMV-specific T cells can effectively target glioblastoma tumor cells for immunologic killing and support the rationale for the development of CMV-directed immunotherapy in patients with GBM., (©2014 American Association for Cancer Research.)

Published
2014
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17. Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.

Author

Sampson JH, Aldape KD, Archer GE, Coan A, Desjardins A, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling R, Shi W, Vredenburgh JJ, Bigner DD, and Heimberger AB

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms therapy, Chemotherapy, Adjuvant, Cohort Studies, DNA Methylation, Dacarbazine adverse effects, Dacarbazine therapeutic use, ErbB Receptors genetics, Female, Glioblastoma therapy, Humans, Hypersensitivity, Delayed, Immunoenzyme Techniques, Lymphopenia drug therapy, Lymphopenia immunology, Male, Middle Aged, Mutation genetics, O(6)-Methylguanine-DNA Methyltransferase genetics, Survival Rate, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory immunology, Temozolomide, Treatment Outcome, Antineoplastic Agents, Alkylating adverse effects, Brain Neoplasms immunology, Dacarbazine analogs & derivatives, ErbB Receptors immunology, Glioblastoma immunology, Lymphopenia chemically induced, Vaccines, Subunit therapeutic use
Abstract

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m(2) per 5 days) or dose-intensified (DI) TMZ (100 mg/m(2) per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/μL). CD3(+) T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (T(Reg); P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI(95): 64.0%-99.8%; P < .0001). The median progression-free survival (15.2 months; CI(95): 11.0-18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI(95): 18.5-33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.

Published
2011
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18. Selective modification of antigen-specific T cells by RNA electroporation.

Author

Mitchell DA, Karikari I, Cui X, Xie W, Schmittling R, and Sampson JH

Subjects
Antigens analysis, Antigens genetics, Brain Neoplasms immunology, Brain Neoplasms therapy, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes transplantation, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes transplantation, Cell Movement, Cells, Cultured, Chemokines metabolism, Dendritic Cells drug effects, Dendritic Cells immunology, Electroporation, Glioma immunology, Glioma therapy, Green Fluorescent Proteins genetics, Humans, Lymphocyte Activation, Peptides genetics, Peptides immunology, Phosphoproteins immunology, Phosphoproteins pharmacology, T-Lymphocytes transplantation, Viral Matrix Proteins immunology, Viral Matrix Proteins pharmacology, Antigens immunology, Immunotherapy, Adoptive methods, RNA, Messenger genetics, Receptors, Interleukin-8B genetics, T-Lymphocytes immunology, Transfection
Abstract

It has been observed that the efficient transfection of T cells by RNA electroporation requires prior activation of T cells with mitogens or by anti-CD3 antibody stimulation. We hypothesized that this requirement for T cell activation could be leveraged to express marker genes within activated T cells responding to antigen-pulsed dendritic cells and allow for the selective enrichment and modification of antigen-specific T cells. Using electroporation of mRNA encoding green fluorescent protein as a marker gene, we demonstrate that RNA electroporation can efficiently allow for the separation of cytomegalovirus-specific CD8+ and CD4+ T cells from bulk culture responding to cytomegalovirus pp65 antigen-pulsed dendritic cells. Furthermore, we demonstrate that cytomegalovirus-specific T cells can be functionally modified by RNA transfection of the C-X-C chemokine receptor, CXCR2, to migrate efficiently toward a variety of CXCR2-specific chemokines in vitro and in vivo. These studies demonstrate the utility of RNA transfection as a simple method by which to purify and selectively modify the function of antigen-specific T cells for use in adoptive immunotherapy, and importantly provide evidence that transient expression of proteins by RNA transfection is an efficient means of modulating the in vivo function of activated T cells.

Published
2008
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19. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma.

Author

Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, and Sampson JH

Subjects
Cytomegalovirus isolation & purification, Cytomegalovirus Infections epidemiology, DNA, Viral analysis, Female, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Polymerase Chain Reaction, Viremia complications, Viremia epidemiology, Brain Neoplasms virology, Cytomegalovirus Infections complications, Glioblastoma virology
Abstract

Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression. In this study, we report on the investigation of detecting HCMV in the tumors and peripheral blood of patients with newly diagnosed glioblastoma multiforme (GBM). Using immunohistochemistry, in situ hybridization, and polymerase chain reaction amplification of viral DNA, the detection of HCMV was investigated in tumor and blood specimens from patients with GBM as well as in the peripheral blood of normal volunteers and patients undergoing craniotomy for diagnoses other than GBM. We found that a high percentage (>90%) of GBM tumors, not surrounding normal brain, are associated with HCMV nucleic acids and proteins. Furthermore, a significant proportion of patients (80%) with newly diagnosed GBM have detectable HCMV DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus, suggesting either a systemic reactivation of HCMV within patients with GBM or shedding of viral DNA from infected tumor cells into the periphery. These results confirm the association of HCMV with malignant gliomas and demonstrate that subclinical HCMV viremia (presence of viral DNA in blood without clinical symptoms of infection) is a previously unrecognized disease spectrum in patients with GBM.

Published
2008
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20. Effective purging of autologous hematopoietic stem cells using anti-B-cell monoclonal antibody-coated high-density microparticles prior to high-dose therapy for patients with non-Hodgkin's lymphoma.

Author

Webb IJ, Friedberg nW, Gribben JG, Fisher DC, Spitzer T, Neuberg D, Jallow H, Kim H, Houde H, Monroy R, Schmittling R, and Freedman AS

Subjects
Adult, Antibodies, Monoclonal therapeutic use, Antigens, Differentiation, B-Lymphocyte immunology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Disease-Free Survival, Graft Survival, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cell Transplantation standards, Humans, Lymphoma, B-Cell pathology, Microspheres, Middle Aged, Pilot Projects, Secondary Prevention, Transplantation, Autologous methods, Transplantation, Autologous standards, B-Lymphocytes cytology, B-Lymphocytes immunology, Cell Separation methods, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cells cytology, Lymphoma, B-Cell therapy
Abstract

Contamination of hematopoietic stem cells (HSCs) with tumor cells has been associated with increased incidence of relapse in patients with non-Hodgkin's lymphoma following autologous HSC transplantation. Effective purging of tumor cells may improve the results of HSC transplantation, but current methods of purging are technically difficult to perform with large numbers of cells and do not consistently remove all detectable cells. We report a pilot clinical trial in which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high-density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by immunocytochemical analysis of the apheresis products prior to treatment. Following treatment with the BCell-HDM, no B-cells were detected in the products from 5 of these patients, a result representing a median depletion of >2.2 logs (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion was 73% for CD34 cells and 78% for CD3+ cells. All patients received high-dose cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B-cell-depleted autologous HSCs. The median number of CD34+ cells cryopreserved was 3.6 x 10(6) cells/kg (range, 2.2-10.1 x 10(6) cells/kg). Engraftment was rapid in all cases, with a median time to achieve an absolute neutrophil count of 0.5 x 10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8-17 days). This nonmagnetic negative-depletion technology is simple, rapid, and effective in depleting target cells to undetectable levels, with excellent recovery of nontarget cells.

Published
2002
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21. Expression of proliferation-associated antigens (PCNA, p120, p145) during the reentry of G0 cells into the cell cycle.

Author

Bolton WE, Freeman JW, Mikulka WR, Healy CG, Schmittling RJ, and Kenyon NS

Subjects
Animals, Base Sequence, Biomarkers, CHO Cells cytology, Cell Cycle, Cell Division, Cricetinae, Fluorescent Antibody Technique, Humans, Molecular Sequence Data, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Tumor Cells, Cultured, tRNA Methyltransferases, Flow Cytometry, Interphase, Nuclear Proteins analysis, Proliferating Cell Nuclear Antigen analysis, S Phase
Abstract

Flow cytometric bivariate analysis was used to evaluate the expression of PCNA, p120, and p145 during the G0 reentry of CHO-K1 cells into the cell cycle. CHO-K1 cells were placed in a G0-like state using serum depletion and stimulated to reenter the cell cycle by replating into fresh, serum-containing medium. At discrete intervals after stimulation, replicate samples were stained for either PCNA, p120, or 145; stained for DNA (Coulter DNA-Prep); evaluated on the EPICS Profile I; and analyzed on the EPICS ELITE workstation. PCNA stained less than 10% of the G0 cells; in contrast, however, 30-35% of the G0 cells were positive for p120 and p145. Eight hours after stimulating G0 cells to reenter the cell cycle (during G0/G1), p120 reached 88% positivity, while p145 and PCNA were 63% and 30% positive, respectively. Cells in S phase (12 and 16 h following G0 stimulation) were greater than 90% positive for all three antigens. PCNA had the greatest change throughout the G0 reentry process, both in percentage positive and quantitatively (mean channel fluorescence). This report indicates that all three proliferation-associated antigens studied are differentially expressed during the reentry of G0 cells into the cell cycle. Furthermore, these antigens may be useful in the early detection of G0 recruitment.

Published
1994
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22. Enhanced assessment of DNA/proliferative index by depletion of tumor infiltrating leukocytes prior to monoclonal antibody gated analysis of tumor cell DNA.

Author

Kenyon NS, Schmittling RJ, Siiman O, Burshteyn A, and Bolton WE

Subjects
Breast Neoplasms chemistry, Breast Neoplasms pathology, Cell Division, Fibroblasts, Fluorescent Antibody Technique, Humans, Leukocyte Common Antigens analysis, Leukocytes, Lung, Ploidies, Tumor Cells, Cultured, Antibodies, Monoclonal, DNA, Neoplasm analysis, Flow Cytometry, Keratins analysis, Lymphocytes, Tumor-Infiltrating, Mitotic Index, Neoplasm Proteins analysis
Abstract

Flow cytometry has become an important tool for the analysis of breast tumors, and assessment of S phase fraction and DNA ploidy are potential indicators of tumor aggression. Due to masking or dilution of infrequent tumor cell events, the presence of normal cell types, such as inflammatory cells and fibroblasts, can interfere with accurate DNA analysis of solid tumor samples. MDA-MB-175-VII human breast carcinoma cells, WI-38 human lung fibroblast cells, and peripheral blood leukocytes were mixed, in varying proportions, in order to represent human breast tumor samples. The cells were subsequently treated with CD45 conjugated magnetic microspheres to deplete tumor infiltrating leukocytes, thus enriching for tumor cells. The tumor cell mixtures were then stained with a pan-cytokeratin specific monoclonal antibody or with a monoclonal antibody that reacts with breast epithelial membrane antigen (EMA). When used in combination with monoclonal antibody gating, utilization of this bead-based technology resulted in enhanced precision of DNA analysis.

Published
1994
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23. Depletion of infiltrating leukocytes and identification of normal fibroblasts prior to the proliferative assessment of rare event tumor cells.

Author

Schmittling R, Siiman O, Kenyon N, and Bolton W

Subjects
Breast Neoplasms pathology, Cell Line, Female, Fibroblasts, Flow Cytometry methods, Humans, Leukocyte Common Antigens immunology, Magnetics, Neoplasms immunology, Tumor Cells, Cultured, Lymphocyte Depletion methods, Lymphocytes immunology, Lymphocytes, Tumor-Infiltrating pathology, Neoplasms pathology
Published
1993
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24. Expression of proliferation associated antigens in the cell cycle of synchronized mammalian cells.

Author

Bolton WE, Mikulka WR, Healy CG, Schmittling RJ, and Kenyon NS

Subjects
Animals, CHO Cells immunology, Cell Division physiology, Cells, Cultured, Cricetinae, DNA analysis, DNA genetics, Flow Cytometry, Fluorescence, G1 Phase physiology, Gene Expression physiology, Nuclear Proteins genetics, Proliferating Cell Nuclear Antigen, Resting Phase, Cell Cycle physiology, S Phase, Staining and Labeling, Nuclear Proteins analysis
Abstract

Flow cytometric bivariate analysis was used to investigate the expression of PCNA, p120 and p145 during the cell cycle of a mammalian cell line (CHO-K1). Initially, aliquots of cells in exponential and plateau (G0) phase were analyzed for proliferation associated antigen expression. Expression of PCNA and p145 during G0 was markedly depressed (less than 12% positive) while 54% of the G0 cells stained positive for p120. The fluorescent intensity (mean channel fluorescence) of these G0 positive p120 cells, however, was only slightly above the mean channel fluorescence (MCF) of cells stained with a negative isotype control. In asynchronous cultures, all three antigens were expressed in greater than 70% of the cells, with PCNA staining being greater than 95%. Cells were then synchronized using mitotic selection (mitotic index of 97%) and antigen levels were measured as cells progressed synchronously through the cell cycle. From DNA analysis histograms, it appeared that the degree of synchrony was approximately 90% throughout the remainder of the cell cycle. The bivariate DNA/PCNA, DNA/p120, and DNA/p145 histograms for mitotic cells indicated that both p120 and p145 expression were elevated (percent positive and MCF) while PCNA levels were near controls (MCF). In early G1, all three markers were depressed (less than 12% positive); however PCNA levels rose precipitously in mid-G1 (greater than 50% positive). In late G1 to early S, p145 levels increased concomitantly with increases in p120. All three antigens were elevated throughout S phase and began to decline as cells moved from G2/M to G1 of the next cell cycle with p145 expression decreasing first. This report indicates that all three proliferation associated antigens studied are differentially expressed in the cell cycle and therefore may be useful in detecting and assessing the proliferation state.

Published
1992
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