Cancer Res. 2024 Dec 2;84(23):4066-4080. doi: 10.1158/0008-5472.CAN-24-0195.

题目：

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

作者：

Licui Jiang1#; Fengtao You2#; Hai Wu1; Changsong Qi3; Shufen Xiang2; Ping Zhang4; Huimin Meng2; Min Wang4; Jiequn Huang2; Yafen Li2; Dan Chen2; Gangli An1; Nan Yang2; Bozhen Zhang2,4; Lin Shen3; Lin Yang1,2,4*

单位：

Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China;

PersonGen BioTherapeutics (Suzhou) Co., Ltd., P. R. China;

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China;

PersonGen.Anke Cellular Therapeutics Co., Ltd.，Hefei, Anhui 230088, China.

# Co-first authors contributed equally to this article.

*Corresponding author

摘要：

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-CAR-modified Vδ1T cells in treating solid tumors. Co-expression of interleukin-2 with the B7-H3-CAR led to durable anti-tumor 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.