Wittrup K Dane
Biological Engineering and Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Trends Cancer. 2017 Sep;3(9):615-620. doi: 10.1016/j.trecan.2017.07.001. Epub 2017 Jul 29.
The classical view of therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) is that their mechanism of action is dominated by signal blocking or the cytotoxicity of Fc-driven innate immune effector functions. We review here a mounting body of evidence that anti-TAA mAbs are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment. Efficient exploitation of these mechanisms has tremendous therapeutic potential.
针对肿瘤相关抗原（TAA）的治疗性单克隆抗体（mAb）的传统观点是，其作用机制主要由信号阻断或Fc驱动的固有免疫效应功能的细胞毒性主导。我们在此回顾越来越多的证据表明，抗TAA单克隆抗体能够与T细胞导向的免疫疗法（如检查点阻断和过继性细胞疗法）产生深刻的协同作用。这种协同作用有两个关键因素：（i）由树突状细胞（DC）介导的自我疫苗效应；（ii）肿瘤微环境的炎症性重极化。有效利用这些机制具有巨大的治疗潜力。
