B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors.

IF 12.5 1区 医学 Q1 ONCOLOGY
Licui Jiang, Fengtao You, Hai Wu, Changsong Qi, Shufen Xiang, Ping Zhang, Huimin Meng, Min Wang, Jiequn Huang, Yafen Li, Dan Chen, Gangli An, Nan Yang, Bozhen Zhang, Lin Shen, Lin Yang
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引用次数: 0

Abstract

Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen presentation pathway, making them a potential "off-the-shelf" cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3 chimeric antigen receptor (CAR)-modified Vδ1T cells in treating solid tumors. Coexpression of IL2 with the B7-H3-CAR led to durable antitumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells. Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors. Significance: A clinical-grade expansion protocol enabled generation of B7-H3-targeted CAR-Vδ1T cells with robust anticancer activity and a favorable safety profile, supporting the potential of CAR-Vδ1T cells as an "off-the-shelf" therapy for solid tumors.

B7-H3靶向CAR-Vδ1T细胞对实体瘤具有强效广谱活性
Vδ1T细胞是γδT细胞的一个罕见亚群,有望用于治疗实体瘤。与传统的 T 细胞不同,它们能独立于 MHC 抗原递呈途径识别肿瘤抗原,因此有可能成为 "现成的 "细胞疗法产品。然而,Vδ1T 细胞的分离和活化具有挑战性,这限制了它们的临床研究。在这里,我们开发了一种大规模临床级 Vδ1T 细胞制造工艺,并验证了 B7-H3-CAR 修饰的 Vδ1T 细胞在治疗实体瘤方面的治疗潜力。白细胞介素-2与B7-H3-CAR的联合表达使Vδ1T细胞在体外和体内具有持久的抗肿瘤活性。在多个皮下和正位小鼠异种移植肿瘤模型中,单次静脉注射 CAR-Vδ1T 细胞可使肿瘤完全消退。这些经过修饰的细胞在体内具有明显的扩增能力和强大的肿瘤归巢能力,类似于天然组织驻留免疫细胞。此外,B7-H3-CAR-Vδ1T 细胞还具有良好的安全性。总之,B7-H3-CAR修饰的Vδ1T细胞是一种治疗实体瘤的有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer research
Cancer research 医学-肿瘤学
CiteScore
16.10
自引率
0.90%
发文量
7677
审稿时长
2.5 months
期刊介绍: Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research. With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445. Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.
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