肿瘤细胞治疗研究
英文原题：Construction and characterization of a novel secreted MsC-CAR-T cell in solid tumors.
CD47-SIRP 信号已被认为是重要的免疫检查点，阻断 CD47 已被证明是治疗实体瘤的一种潜在治疗策略。
CD47-SIRP信号通路已被确认为重要免疫检查点，阻断CD47被证实是治疗实体瘤的潜在策略。然而，CAR-T细胞同时分泌抗体片段以治疗实体瘤的潜在应用很少得到探索。本研究检索生物信息学数据库并分析CD47在实体瘤中的特征，随后利用数据库信息设计、优化并构建了一种新型MsC-CAR，可靶向MAGE-A1并自行分泌CD47-scFv。研究制备了含MsC-CAR的工程化T细胞，并对其进行转染、验证和表征；随后在体外和体内评估MsC-CAR-T细胞的抑瘤作用。结果显示，MsC-CAR成功构建，其中MsC1-CAR具有较佳特性，能够识别MAGE-A1并分泌CD47-scFv。表达MsC1-CAR的工程化T细胞（MsC1-CAR-T细胞）在多种癌细胞系及肺腺癌（LUAD）异种移植瘤中均表现出突出的抑瘤效力。本研究数据显示，MsC1-CAR-T细胞将过继细胞免疫治疗与免疫检查点抑制剂疗法精巧结合，可能为治疗MAGE-A1阳性实体瘤提供新方向。
The CD47-SIRP signaling has been acknowledged as a significant immune checkpoint and CD47 blocking has been proved as a potential therapeutic strategy for the treatment of solid tumor. However, the potential application of CAR-T cells secreted antibody fragment simultaneously in solid tumor is rarely explored. In this study, we searched bioinformatic databases and investigated the characteristics of CD47 in solid tumors. Then we consulted bioinformatic databases to design, optimize and construct a novel MsC-CAR which could target MAGE-A1 and self-secrete CD47-scFv. The engineering T cells containing MsC-CAR were transfected, verified and characterized. The tumor-inhibitory role of MsC-CART cells was further determined in vitro and in vivo. The results showed that MsC-CARs were successfully constructed and MsC1-CARs demonstrated the preferable features of recognizing MAGE-A1 and secreting CD47-scFv. Engineering T cells transfecting with MsC1-CAR (MsC1-CART cells) exerted the prominent tumor-inhibitory effectiveness, both in different cancer cell lines and LUAD xenograft tumors. The present data highlighted that MsC1-CART cells elaborately combined the adoptive cellular immunotherapy and immune checkpoint inhibitor therapy, may represent a new direction for the treatment of MAGE-A1 positive solid tumors.
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