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:Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues.
Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues.
本研究在体外和体内评估了异体 i T 细胞对细胞系和类器官的细胞毒性。
多种免疫疗法已用于治疗恶性肿瘤,自体 CAR-T 细胞疗法也已用于部分恶性肿瘤,但其对实体瘤的疗效有限。T 细胞具有强效肿瘤细胞毒性,且其活性不受 MHC 限制。我们成功从 iPS 细胞诱导获得 T 细胞,并证实其在体外可杀伤结直肠癌细胞系。然而,癌细胞系往往缺乏肿瘤异质性和药物敏感性等关键特征。相比之下,患者来源癌症类器官能保留患者肿瘤组织的许多特点。本研究在体外和体内评估了异基因 iT 细胞对细胞系及类器官的细胞毒作用。体外实验中,iT 细胞对细胞系和类器官的细胞毒性为 70%–90%。体内局部或静脉给予 iT 细胞,可使肿瘤生长抑制 70%–100%,凸显其作为结直肠癌新型免疫疗法的潜力。
Various immunotherapies have been developed to treat malignant tumors, and autologous CAR-T cell therapy is clinically used for certain malignancies. However, their efficacy against solid tumors is limited. T cells are recognized for their potent tumor cytotoxicity and MHC-unrestricted activity. We successfully induced T cells from iPS cells and demonstrated their cytotoxicity against colorectal cancer cell lines in vitro. However, cancer cell lines often lack critical tumor characteristics such as heterogeneity and drug sensitivity. In contrast, patient-derived cancer organoids retain many features of the patient's tumor tissues. This study evaluated the cytotoxicity of allogeneic i T cells against cell lines and organoids, in vitro and in vivo. i T cells showed 70%-90% cytotoxicity against cell lines and organoids in vitro. In vivo, local and intravenous administration of i T cells suppressed tumor growth by 70%-100%, highlighting their potential as a novel immunotherapy for colorectal cancer.
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