CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies.
Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies.
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γδ T 细胞约占外周血淋巴细胞的 5%-10%,在肿瘤免疫监视中发挥关键作用,并且常富集于上皮组织内。其独特之处在于通过 γδ T 细胞受体(TCR)以及固有受体以 主要组织相容性复合体 非依赖的方式识别抗原,使其成为异体“现货型”细胞治疗产品的理想候选者。在人类中,已定义了 γδ T 细胞的两个主要结构亚群——Vδ1 和 Vδ2——它们在 TCRδ 链、效应功能和组织定位方面存在差异。Vδ2 T 细胞构成外周血中 γδ T 细胞的大多数,并可通过氨基双膦酸盐如 zoledronic acid 进行扩增。近年来,Vδ1 T 细胞的强效抗肿瘤功能也已被认识到,新的扩增方案正在开发中。鉴于 γδ T 细胞对血液系统恶性肿瘤疗效的大量临床前证据,目前已有多个基于 γδ T 细胞的细胞治疗产品处于临床开发阶段,并且过继性 γδ T 细胞治疗临床试验的数量呈指数增长。这篇综合性综述概述了 γδ T 细胞治疗的理论依据、正在进行的临床试验,以及基于 γδ T 细胞的免疫治疗在血液学中的挑战和未来作用。
Gamma delta (γδ) T cells, which constitute about 5%-10% of peripheral blood lymphocytes, play key roles in tumor immunosurveillance and are often enriched within epithelial tissues. They are unique in their Major Histocompatibility Complex-independent antigen recognition via the γδ T-cell receptor (TCR) as well as via innate receptors, making them ideal1 candidates for allogeneic "off-the-shelf" cell therapy products. In humans, two main structural subsets of γδ T cells-Vδ1 and Vδ2-have been defined, which differ in TCRδ chains, effector function, and tissue localizations. Vδ2 T cells constitute the majority of γδ T cells in peripheral blood and can be expanded with aminobisphosphonates such as zoledronic acid.
In recent years, the potent antitumor functions of Vδ1 T cells have also been recognized, and new expansion protocols are being developed. Given the ample preclinical evidence of γδ T-cell efficacy against hematological malignancies, several γδ T-cell-based cell therapy products are currently in clinical development, and there has been an exponential increase in the number of adoptive γδ T-cell therapy clinical trials.
This comprehensive review provides an overview of the rationale for γδ T-cell therapy, ongoing clinical trials, as well as the challenges and future role of γδ T-cell-based immune therapies in hematology.
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