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Protective Antitumor Immunity Induced by a Costimulatory Thalidomide Analog in Conjunction with Whole Tumor Cell Vaccination Is Mediated by Increased Th1-Type Immunity

Thalidomide and its novel T cell costimulatory analogs (immunomodulatory drugs) are currently being assessed in the treatment of patients with advanced cancer. However, neither tumor-specific T cell costimulation nor effective antitumor activity has been demonstrated in vivo. In this study, we asses...

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Published in:The Journal of immunology (1950) 2002-05, Vol.168 (10), p.4914-4919
Main Authors: Dredge, Keith, Marriott, J. Blake, Todryk, Stephen M, Muller, George W, Chen, Roger, Stirling, David I, Dalgleish, Angus G
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container_title The Journal of immunology (1950)
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Dalgleish, Angus G
description Thalidomide and its novel T cell costimulatory analogs (immunomodulatory drugs) are currently being assessed in the treatment of patients with advanced cancer. However, neither tumor-specific T cell costimulation nor effective antitumor activity has been demonstrated in vivo. In this study, we assessed the ability of an immunomodulatory drug (CC-4047/ACTIMID) to prime a tumor-specific immune response following tumor cell vaccination. We found that the presence of CC-4047 during the priming phase strongly enhanced antitumor immunity in the vaccinated group, and this correlated with protection from subsequent live tumor challenge. Protection was associated with tumor-specific production of IFN-gamma and was still observed following a second challenge with live tumor cells 60 days later. Furthermore, CD8(+) and CD4(+) splenocyte fractions from treated groups secreted increased IFN-gamma and IL-2 in response to tumor cells in vitro. Coculture of naive splenocytes with anti-CD3 mAb in the presence of CC-4047 directly costimulated T cells and increased Th1-type cytokines. Our results are the first to demonstrate that a costimulatory thalidomide analog can prime protective, long-lasting, tumor-specific, Th1-type responses in vivo and further support their ongoing clinical development as novel anti-cancer agents.
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ispartof The Journal of immunology (1950), 2002-05, Vol.168 (10), p.4914-4919
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subjects Adjuvants, Immunologic - administration & dosage
Animals
Antigens, CD - biosynthesis
Antineoplastic Combined Chemotherapy Protocols - immunology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
B7-1 Antigen - biosynthesis
B7-2 Antigen
Cancer Vaccines - administration & dosage
Cancer Vaccines - immunology
Cells, Cultured
Coculture Techniques
Cytokines - biosynthesis
Growth Inhibitors - administration & dosage
Growth Inhibitors - immunology
Histocompatibility Antigens Class I - biosynthesis
Injections, Intraperitoneal
Injections, Subcutaneous
Interferon-gamma - biosynthesis
Melanoma, Experimental
Membrane Glycoproteins - biosynthesis
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Neoplasm Transplantation - immunology
Spleen - cytology
Spleen - immunology
Spleen - metabolism
T-Lymphocyte Subsets - immunology
Th1 Cells - immunology
Thalidomide - administration & dosage
Thalidomide - analogs & derivatives
Tumor Cells, Cultured - immunology
Tumor Cells, Cultured - metabolism
Tumor Cells, Cultured - pathology
Tumor Cells, Cultured - transplantation
title Protective Antitumor Immunity Induced by a Costimulatory Thalidomide Analog in Conjunction with Whole Tumor Cell Vaccination Is Mediated by Increased Th1-Type Immunity
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