小分子肿瘤免疫治疗药物研究进展

The research progress of small molecule immuno-oncology therapeutic agents

近年来,以免疫检查点抑制剂和嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)治疗为代表的肿瘤免疫疗法取得了突破性的进展,并迅速改变了肿瘤治疗的模式。然而,临床随访数据表明,并不是所有患者都能从单克隆抗体免疫疗法中获益。与大多数抗体药物相比,小分子药物有更好的组织渗透性,可以直接靶向固有或适应性免疫细胞的检查点蛋白下游细胞内通路。未来,小分子免疫疗法或可作为抗体药物的补充或联合抗体药物来促进抗肿瘤免疫反应效果或克服耐药问题。本文对进入临床研发阶段的小分子肿瘤免疫治疗药物及其作用机制进行系统介绍。

In recent years, tumor immunotherapy such as immune checkpoint inhibitors and CAR-T cell therapy has made breakthroughs and greatly changed the mode of cancer treatment. However, follow-up data in clinical showed that not all patients benefited from the monoclonal antibody therapy. Small molecules can easily penetrate into tissues compared with most antibodies and therefore be directed towards downstream checkpoint proteins of intracellular pathway in innate or adaptive immune cells. In the future, small-molecule immunotherapy has the potential to complement existing therapeutic antibodies and be used in combination with antibodies to promote antitumor immunity or address drug resistance. In this review, we summarize the small molecule immuno-oncology agents in clinical trials based on their targets.