[关键词]
[摘要]
[摘要] 以嵌合抗原受体T细胞(CAR-T)为代表的基因编辑T细胞在血液肿瘤中取得了卓越的成效,并逐渐应用在肿瘤的临床治疗中。2017 年,先后有两款针对血液肿瘤的CAR-T细胞产品在美国获批上市,越来越广泛地应用在于实体肿瘤的治疗。但是利用CAR-T技术治疗实体瘤却遇到一些困境,实体瘤特有的微环境和表面肿瘤抗原的限制导致CAR-T细胞治疗效果并不理想,脱靶效应造成的细胞毒性更为棘手。针对这一问题,越来越多的研究人员开始探索新型的基因编辑T细胞用于实体瘤的治疗,其中双特异性T细胞衔接子基因编辑的T细胞(BiTE-T)在体外评估以及体内动物模型中展现出高效的抗肿瘤效果引起了高度关注。本文主要论述目前实体瘤治疗面临的困境以及BiTE-T细胞制备的原理、特点和应用于实体瘤治疗的优势。
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[Abstract]
[Abstract] Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment.However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles,characteristics and advantages of BiTE-T cell preparation.
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[基金项目]
国家自然科学基金资助项目(No. 31570892, No.31770992, No. 81730045);国家“精准医学研究”重点研发计划(No.2017YFC0909800);国家科技重大专项(No. 2017ZX10203207)