CAR技术在多发性骨髓瘤治疗领域的研究进展

CAR Technology and Its Application in Treatment of Multiple Myeloma

多发性骨髓瘤(multiple myeloma,MM)是在B淋巴细胞分化为浆细胞过程中因遗传基因发生突变所致的血液系统恶性肿瘤,化疗是目前主要治疗的手段;随着蛋白酶体抑制剂等药物的开发,患者的总体生存率得到了提高,但耐药等因素仍然会导致治疗的失败。嵌合抗原受体(chimeric antigen receptor,CAR)修饰的T淋巴细胞治疗是近5年来肿瘤过继免疫治疗的新方法,通过基因修饰的手段,使T细胞能够能特异性识别靶抗原,并以非组织相容性抗原(major histocompatibility complex,1VIHC)限制性的方式杀伤靶细胞,从而产生特异性的杀伤作用。目前,CAR-T治疗越来越被人们所关注,尤其在B系来源的白血病和淋巴瘤中取得了惊人的成绩。然而就多发性骨髓瘤的CAR技术治疗而言,未见系统的文献复习。因此,本文就可查阅到的以不同靶点的CAR技术在多发性骨髓瘤体内及体外实验中所获得的研究成果作一综述。

Multiple myeloma(MM) is a hematologic malignancy resulted from genetic mutations in the process of B lymphocyte differentiating into plasma cells,the chemotherapy is the main treatment method,especially with the development of proteasome inhibitors and other drugs,the overall survival rate of MM patients has improved greatly,but the chemoresistance is still an important reason for treatment failure.Chimeric antigen receptor(CAR)- modified T lymphocyte therapy is a new method for tumor adoptive immunotherapy.By means of genetic modification,T cells are able to identify the target antigen specifically,and to kill target cells without major histocompatibility complex(MHC)restriction,therefore the specific killing activity is conspicuous,which has got considerable attention by the public,and has made remarkable achievements particularly in the treatment of B4 ineage leukemia and lymphoma,but no systematic literatures were reported in the field of multiple myeloma using CAR therapy.Therefore,this review summarizes the research results of different CAR target in vivo and in vitro experiments for multiple myeloma.