CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering.
Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering.
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异体Vγ9Vδ2（Vδ2）T细胞因其在异体环境中已确立的安全性以及固有的抗肿瘤能力，已成为开发癌症疗法的有吸引力的候选者。
然而，基于Vδ2 T细胞的治疗在临床上有限的成功可能归因于供者差异、体内持久性短暂以及肿瘤免疫逃逸。为解决这些限制，我们对Vδ2 T细胞进行工程改造以增强其特性。通过采用CD16作为供者选择生物标志物，我们利用具有增强细胞毒性和强效抗体依赖性细胞介导的细胞毒性（ADCC）功能的Vδ2 T细胞。RNA测序分析支持来源于CD16高（CD16 Hi）供者的Vδ2 T细胞具有增强的效应潜能。通过CAR和IL-15工程改造方法进一步实现了显著提升。在两种卵巢癌模型中的临床前研究证实了工程化CD16 Hi 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，且不引发移植物抗宿主病。这些发现强调了工程化CD16 Hi Vδ2 T细胞作为癌症治疗可行选择的潜力。
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 (CD16 Hi ) 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 CD16 Hi 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 CD16 Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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