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.

中文翻译：

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B7-H3 靶向 CAR-Vδ1T 细胞对实体瘤表现出有效的广谱活性


Vδ1T 细胞是 γδT 细胞的一种罕见亚群，有望治疗实体瘤。与传统 T 细胞不同，它们独立于 MHC 抗原呈递通路识别肿瘤抗原，使其成为潜在的“现成”细胞治疗产品。然而，Vδ1T 细胞的分离和激活具有挑战性，这限制了它们的临床研究。在这里，我们开发了一种用于 Vδ1T 细胞的大规模临床级制造工艺，并验证了 B7-H3-CAR 修饰的 Vδ1T 细胞在治疗实体瘤中的治疗潜力。白细胞介素-2 与 B7-H3-CAR 的共表达导致 Vδ1T 细胞在体外和体内具有持久的抗肿瘤活性。在多个皮下和原位小鼠异种移植肿瘤模型中，单次静脉内施用 CAR-Vδ1T 细胞导致肿瘤完全消退。这些修饰的细胞表现出显著的体内扩增和对肿瘤的强大归巢能力，类似于天然组织驻留免疫细胞。此外，B7-H3-CAR-Vδ1T 细胞表现出良好的安全性。总之，B7-H3-CAR 修饰的 Vδ1T 细胞代表了治疗实体瘤的一种有前途的策略。