决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CAR-NK cells in combination therapy against cancer: A potential paradigm.
多种临床前研究以及有限数量的临床研究显示,CAR-NK细胞取得了有希望的结果:能有效清除靶细胞,且不会出现类似CAR-T疗法的副作用。
多种临床前研究和有限数量的CAR-NK细胞临床研究已显示出有希望的结果:有效消除靶细胞,且无类似于CAR-T治疗的副作用。然而,由于抑制性肿瘤微环境,CAR-NK细胞的归巢和浸润能力较差。从临床治疗策略的角度来看,结合NK细胞的生物学和肿瘤微环境特征,CAR-NK联合抗PD-1/PD-L1、放疗和化疗、激酶抑制剂、蛋白酶体抑制剂、STING激动剂、溶瘤病毒、光热疗法的联合治疗策略,可以极大地促进NK细胞的增殖、迁移和细胞毒性。在这篇综述中,我们将总结CAR-NK细胞用于肿瘤的靶点选择、结构构建和联合治疗,以提供可行的联合策略,用于克服抑制性肿瘤微环境并提高CAR-NK细胞的疗效。
Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.
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