Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Cancer Res. 2011 Nov 1;71(21):6567-71. doi: 10.1158/0008-5472.CAN-11-1487. Epub 2011 Oct 18.
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.
对 T 细胞激活和增殖控制的新认识导致了检查点蛋白的鉴定，这些蛋白可以上调或下调 T 细胞反应性。与细胞毒性 T 淋巴细胞抗原 4 或程序性死亡受体 1 反应的单克隆抗体免疫疗法在患有已建立的癌症的小鼠和人类中显示出有希望的治疗结果，这突出表明使用 T 细胞检查点抑制剂的癌症免疫疗法是最有前途的新治疗方法之一。T 细胞免疫球蛋白和粘蛋白结构域 3（TIM3）是许多类似的抑制性分子之一，作为靶点越来越受到关注，但在肿瘤学中相对研究较少。这篇综述讨论了我们最近在探讨针对小鼠中已建立的自发性和实验性肿瘤的抗 TIM3 抗体的作用机制，这是一个令人兴奋的可能性，即合理地联合促进肿瘤特异性 T 细胞激活、增殖、效应功能和存活的药物。
