靶向Tim-3药物研发进展

肿瘤微环境可诱导一些免疫检查点分子的高表达,以利于肿瘤细胞逃避免疫系统的识别和攻击.目前基于程序性死亡受体1(programmed cell death protein 1,PD-1)、细胞毒性T淋巴细胞相关抗原4(cytotoxic T-lymphocyte associated protein 4,CTLA-4)以及T细胞免疫球蛋白黏蛋白3(T-cell immunoglobulin and mucin domain-containing protein 3,Tim-3)等免疫检查点分子的靶向抗体药物研发已经取得了极大的进展,其中多种靶向PD-1和CTLA-4的抗体药物已被美国食品药品监督管理局(Food andDrug Administration,FDA)批准上市,虽然有部分患者经以上药物治疗后出现完全缓解或生存期延长,但尚存在较多患者出现耐药或没有缓解病情的状况.最新的研究发现,靶向PD-1治疗的耐药患者Tim-3表达上调,Tim-3也被认为是潜在的新一代肿瘤治疗靶点,Tim-3与PD-1的靶向联合治疗有可能成为研究的热点.现就国内外靶向Tim-3药物的研究现状做一综述.

Progress in research and development of targeted Tim-3 drugs

The tumor microenvironment can induce high expression of some immune checkpoint molecules to facilitate tumor cells to escape from the recognition and attack of the immune system.At present,great progress has been made in the research and development of targeted antibody drugs based on programmed cell death protein 1(PD-1),cytotoxic T-lymphocyte associated protein 4(CTLA-4),T-cell immunoglobulin and mucin domain-containing protein 3(Tim-3).Many of the antibody drugs targeting PD-1 and CTLA-4 have been approved by the Food and Drug Administration(FDA).Although some patients have had a complete remission or prolonged survival after the treatment of drugs above,there are still many patients showing drug resistance or no remission.Recent study found that Tim-3 expression was up-regulated in PD-1-targeted drug-resistant patients,and was also considered as a potential new generation of tumor treatment target.Therefore the targeted combination therapy of Tim-3 and PD-1 is taken into consideration.At the same tiame,Tim-3 is also considered as a potential next-generation treatment target for tumor.This review will mainly introduce the research status of Tim-3 targeted drugs in tumor therapy.