同种异体 Vγ9Vδ2 (Vδ2) T 细胞因其在同种异体环境中已确定的安全性和固有的抗肿瘤能力而成为开发癌症治疗的有吸引力的候选者。尽管如此，基于 Vδ2 T 细胞的治疗的临床成功有限可能归因于供体变异性、短暂的持续性和肿瘤免疫逃避。为了解决这些限制，我们设计了具有增强属性的 Vδ2 T 细胞。通过使用 CD16 作为供体选择生物标志物，我们利用了 Vδ2 T 细胞，其特征是增强的细胞毒性和有效的抗体依赖性细胞介导的细胞毒性 (ADCC) 功能。 RNA 测序分析支持来自 CD16 高 (CD16Hi) 供体的 Vδ2 T 细胞的增强效应潜力。通过 CAR 和 IL-15 工程方法进一步实现了实质性增强。对两种卵巢癌模型的临床前研究证实了工程 CD16Hi Vδ2 T 细胞的有效性和安全性。这些细胞通过多种机制靶向肿瘤，表现出持续的体内持久性，并且不会引起移植物抗宿主病。这些发现强调了工程化 CD16Hi Vδ2 T 细胞作为癌症治疗的可行治疗选择的前景。© 2023。作者。

Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.© 2023. The Author(s).