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:Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer.
Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer.
约 20-30% 的乳腺癌患者在根治性手术切除后发生侵袭或转移,并最终死亡。
乳腺癌是女性最常见的癌症。约 20%–30% 患者在根治性手术切除后发生侵袭或转移,最终死亡。尽管化疗、内分泌治疗和分子靶向治疗取得进展,仍有相当数量患者对治疗敏感性较差。持续治疗过程中会出现耐药、肿瘤复发或转移,因此需要有利的治疗策略。嵌合抗原受体(CAR)修饰 T 细胞疗法已成为肿瘤免疫治疗的一部分。然而,CAR-T 治疗实体瘤疗效不佳,原因包括肿瘤微环境复杂、细胞外基质抑制作用以及缺乏理想肿瘤抗原。本文讨论 CAR-T 细胞疗法治疗转移性乳腺癌的前景,并回顾临床阶段乳腺癌 CAR-T 治疗靶点(HER-2、C-MET、MSLN、CEA、MUC1、ROR1 和 EGFR)。此外,针对乳腺癌 CAR-T 治疗的挑战,提出相应解决策略,包括脱靶效应、肿瘤细胞抗原表达异质性和免疫抑制性肿瘤微环境,并提出改善 CAR-T 治疗转移性乳腺癌疗效的思路。
Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested.
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