Anti-TIM3 Antibody Promotes T Cell IFN-γ–Mediated Antitumor Immunity and Suppresses Established Tumors
Open Access
- 15 May 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (10), 3540-3551
- https://doi.org/10.1158/0008-5472.can-11-0096
Abstract
Strategies to activate and rescue exhausted tumor-specific T cells, including the use of monoclonal antibodies (mAb) that block the negative costimulatory receptors CTLA-4 and PD-1 are proving very effective, but TIM3 has been relatively neglected as a target. Here we report an extensive characterization of the therapeutic activity and mechanism of action of an anti-mouse TIM3 mAb against experimental and carcinogen-induced tumors. For the first time we specifically define the mechanism of antitumor action of anti-TIM3 requiring IFN-γ producing CD8+ T cells and CD4+ T cells, and a higher ratio of tumor infiltrating CD8+:CD4+ T cells correlating with therapeutic success. Interestingly, in some models, anti-TIM3 appeared to be effective sometime before the appearance and accumulation of significant TIM3+PD-1+ T cell populations in tumor bearing mice. Anti-TIM3 displayed modest prophylactic and therapeutic activity against a small fraction of carcinogen-induced sarcomas, but comparative and combination studies of anti-TIM3 with anti-CTLA-4 and anti–PD-1 against experimental and carcinogen-induced tumors suggested that these agents might be well-tolerated and very effective in combination. Cancer Res; 71(10); 3540–51. ©2011 AACR.Keywords
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This publication has 34 references indexed in Scilit:
- T-Cell Immunoglobulin Mucin-3 Determines Severity of Liver Ischemia/Reperfusion Injury in Mice in a TLR4-Dependent MannerGastroenterology, 2010
- Anti–CTLA-4 Antibody Therapy: Immune Monitoring During Clinical Development of a Novel ImmunotherapySeminars in Oncology, 2010
- Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunityThe Journal of Experimental Medicine, 2010
- Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patientsThe Journal of Experimental Medicine, 2010
- Features of responding T cells in cancer and chronic infectionCurrent Opinion in Immunology, 2010
- IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasisProceedings of the National Academy of Sciences of the United States of America, 2010
- PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumorsProceedings of the National Academy of Sciences of the United States of America, 2010
- Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patientsProceedings of the National Academy of Sciences of the United States of America, 2008
- Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesisProceedings of the National Academy of Sciences of the United States of America, 2008
- Checkpoint Blockade in Cancer ImmunotherapyAdvances in Immunology, 2006