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2. Autologous peripheral blood mononuclear cell recognition of autologous proliferating tumor cells in the context of a patient-specific vaccine trial

Author

Cornforth, A.N., Lee, G., and Dillman, R.O.

Subjects
Cell proliferation -- Research, Tumors -- Physiological aspects -- Health aspects, Blood -- Physiological aspects -- Health aspects, Cancer vaccines -- Physiological aspects -- Health aspects, Biotechnology industry, High technology industry
Abstract

Metastatic melanoma patients who were treated with patient-specific vaccines consisting of dendritic cells loaded with autologous tumor cells had a 5-year survival of over 50%. Enzyme-linked immunospot (ELISPOT) has been used to detect antigen reactive T cells as a means of determining immune response. We wished to determine whether IFN-gamma secretion in an ELISPOT assay was prognostic or predictive for survival following treatment. Peripheral blood mononuclear cells (PBMCs) collected at weeks 0 and 4 were evaluated by ELISPOT assay for response to autologous tumor cells. Overall, there was slight increase in the number of tumor reactive lymphocytes from week 0 to week 4. Using >5 spots/100 K PBMC as the cutoff, a log-rank analysis revealed only a slight statistical significance in overall survival for patients who lacked tumor reactive PBMCs at week 4. The sensitivity of ELISPOT in the context of patient-specific cellular vaccines is unclear., 1. Introduction Metastatic melanoma is generally considered to be incurable. Immunotherapy is a promising alternative treatment to chemotherapy, but challenges remain in determining response to therapy. Clinical trials that use [...]

Published
2011
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3. Defining the Critical Hurdles in Cancer Immunotherapy

Author

Fox, B.A., Schendel, D.J., Butterfield, L.H., Aamdal, S., Allison, J.P., Ascierto, P.A., Atkins, M.B., Bartunkova, J., Bergmann, L., Berinstein, N., Bonorino, C.C., Borden, E., Bramson, J.L., Britten, C.M., Cao, X., Carson, W.E., Chang, A.E., Characiejus, D., Choudhury, A., Coukos, G., Gruijl, T.D. de, Dillman, R.O., and Dolstra, H.

Subjects
Immune Regulation Translational research [NCMLS 2], GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Contains fulltext : 97787.pdf (Publisher’s version ) (Open Access)

Published
2011

4. Defining the Critical Hurdles in Cancer Immunotherapy

Author

Fox, BA, Schendel, D.J., Butterfield, L.H., Aamdal, S., Allison, J.P., Ascierto, P.A., Atkins, M.B., Bartunkova, J., Bergmann, L., Berinstein, N., Bonorino, C.C., Borden, E., Bramson, J.L., Britten, C.M., Cao, X., Carson, W.E., Chang, A.E., Characiejus, D., Choudhury, A.R., Coukos, G., de Gruijl, T.D., Dillman, R.O., Dolstra, H., Dranoff, G., Durrant, L.G., Finke, J.H., Galon, J., Gollob, J.A., Gouttefangeas, C., Grizzi, F., Guida, M., Hakansson, L., Hege, K., Herberman, R.B., Hodi, F.S., Hoos, A., Huber, C., Hwu, P., Imai, K., Jaffee, E.M., Janetzki, S., June, C.H., Kalinski, P., Kaufmann, H.L., Kawakami, K., Kawakami, Y., Keilholtz, U., Khleif, S.N., Kiessling, R., Kotlan, B., Kroemer, G., Lapointe, R., Levitsky, H.I., Lotze, M.T., Di Maio, M., Marschner, J.P., Mastrangelo, M.J., Masucci, G., Melero, I., Nelief, C., Murphy, W.J., Nelson, B., Nicolini, A., Nishimura, M.I., Odunsi, K., Ohashi, P.S., O'Donnell-Tormey, J., Old, L.J., Ottensmeier, C., Papamichail, M., Parmiani, G., Pawelec, G., Proietti, E., Qin, S., Rees, R., Ribas, A., Ridolfi, R., Ritter, G., Rivoltini, L., Romero, P.J., Salem, M.L., Scheper, R.J., Seliger, B., Sharma, P., Shiku, H., Singh-Jasuja, H., Song, W., Straten, P.T., Tahara, H., Tian, Z., van der Burg, S.H., von Hoegen, P., Wang, E., Welters, M.J., Winter, H., Withington, T., Wolchok, J.D., Xiao, W., Zitvogel, L., Zwierzina, H., Marincola, F.M., Gajewski, T.F., Wigginton, J.M., Disis, M.L.A., Fox, BA, Schendel, D.J., Butterfield, L.H., Aamdal, S., Allison, J.P., Ascierto, P.A., Atkins, M.B., Bartunkova, J., Bergmann, L., Berinstein, N., Bonorino, C.C., Borden, E., Bramson, J.L., Britten, C.M., Cao, X., Carson, W.E., Chang, A.E., Characiejus, D., Choudhury, A.R., Coukos, G., de Gruijl, T.D., Dillman, R.O., Dolstra, H., Dranoff, G., Durrant, L.G., Finke, J.H., Galon, J., Gollob, J.A., Gouttefangeas, C., Grizzi, F., Guida, M., Hakansson, L., Hege, K., Herberman, R.B., Hodi, F.S., Hoos, A., Huber, C., Hwu, P., Imai, K., Jaffee, E.M., Janetzki, S., June, C.H., Kalinski, P., Kaufmann, H.L., Kawakami, K., Kawakami, Y., Keilholtz, U., Khleif, S.N., Kiessling, R., Kotlan, B., Kroemer, G., Lapointe, R., Levitsky, H.I., Lotze, M.T., Di Maio, M., Marschner, J.P., Mastrangelo, M.J., Masucci, G., Melero, I., Nelief, C., Murphy, W.J., Nelson, B., Nicolini, A., Nishimura, M.I., Odunsi, K., Ohashi, P.S., O'Donnell-Tormey, J., Old, L.J., Ottensmeier, C., Papamichail, M., Parmiani, G., Pawelec, G., Proietti, E., Qin, S., Rees, R., Ribas, A., Ridolfi, R., Ritter, G., Rivoltini, L., Romero, P.J., Salem, M.L., Scheper, R.J., Seliger, B., Sharma, P., Shiku, H., Singh-Jasuja, H., Song, W., Straten, P.T., Tahara, H., Tian, Z., van der Burg, S.H., von Hoegen, P., Wang, E., Welters, M.J., Winter, H., Withington, T., Wolchok, J.D., Xiao, W., Zitvogel, L., Zwierzina, H., Marincola, F.M., Gajewski, T.F., Wigginton, J.M., and Disis, M.L.A.

Abstract

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. © 2011 Fox et al; licensee BioMed Central Ltd.

Published
2011
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6. Murine Monoclonal Antibody Therapy in Two Patients With Chronic Lymphocytic Leukemia

Author

Dillman, R.O., Shawler, D.L., Sobol, R.E., Collins, H.A., Beauregard, J.C., Wormsley, S.B., and Royston, I.

Abstract

We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10-15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2-4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.

Published
1982
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