Prospects for TIM3-Targeted Antitumor Immunotherapy.
New insights into the control of T-cell activation and proliferation have led to the identification of checkpoint proteins that either up- or downmodulate T-cell reactivity. Monoclonal antibody immunotherapies that are reactive with cytotoxic T lymphocyte antigen 4 or programmed death receptor 1 have shown promising therapeutic outcomes in mice and humans with established cancer, highlighting the fact that cancer immunotherapy using T-cell checkpoint inhibitors is one of the most promising new therapeutic approaches. T-cell immunoglobulin and mucin domain 3 (TIM3) is one of many similar inhibitory molecules that are gaining attention as targets, but it remains relatively poorly studied in oncology. This review discusses our recent probing of the mechanism of action of anti-TIM3 antibody against established spontaneous and experimental tumors in mice, in the context of the exciting possibility of rationally combining agents that promote tumor-specific T-cell activation, proliferation, effector function, and survival.
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Shin Foong
SF
Ngiow
Michele W L
MW
Teng
Mark J
MJ
Smyth
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D017635:Clonal Anergy / Q000276:immunology; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005544:Forecasting; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D051379:Mice; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011991:Receptors, Virus