文章：

AAV介导的体内CAR基因疗法靶向治疗人类T细胞白血病

AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia

原文发布日期：2021-06-23

DOI: 10.1038/s41408-021-00508-1

类型: Article

开放获取: 是

英文摘要：

Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkdcscid Il2rgem26/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the β processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.
 

摘要翻译： 

嵌合抗原受体（CAR）T细胞疗法是免疫肿瘤学中最活跃的领域，为B细胞恶性肿瘤患者带来显著获益。然而，CAR T细胞生成的复杂流程限制了其广泛应用。本文描述了一种新方法：通过注射携带CAR基因的腺相关病毒（AAV）载体，在宿主体内直接生成人源CAR T细胞，我们称之为AAV递送CAR基因疗法（ACG）。在对人源T细胞白血病的人源化NOD.Cg-Prkdcscid Il2rgem26/Nju肿瘤小鼠模型进行单次输注后，AAV可产生足够数量的强效体内CAR细胞，从而诱导肿瘤消退；这些体内生成的CAR细胞表现出抗肿瘤免疫特性。这种即时生成体内CAR T细胞的方法可能绕过患者淋巴细胞清除的需求，以及传统CAR T细胞生产中的繁琐流程，有望使CAR疗法更简便、更经济。它可能推动以按需治疗和多样化疗法形式发展的复杂个性化治疗方案。

原文链接：

AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia