Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China.
State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, People's Republic of China.
Blood Cancer J. 2021 Jun 23;11(6):119. doi: 10.1038/s41408-021-00508-1.
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-Prkd Il2rg/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.
嵌合抗原受体 (CAR) T 细胞疗法是肿瘤免疫领域最活跃的领域,为 B 细胞恶性肿瘤患者带来了实质性的益处。然而,CAR T 细胞的复杂制备过程限制了其广泛应用。在这里,我们描述了一种新方法,通过注射携带 CAR 基因的腺相关病毒 (AAV) 载体,在宿主中生成人源性 CAR T 细胞,我们称之为 AAV 递送 CAR 基因治疗 (ACG)。在单次输注到人类 T 细胞白血病的人源化 NOD.Cg-Prkd Il2rg/Nju 肿瘤小鼠模型中,AAV 可生成足够数量的有效体内 CAR 细胞,从而导致肿瘤消退;这些体内生成的 CAR 细胞产生抗肿瘤免疫特性。这种体内 CAR T 细胞的即时生成可能不需要患者进行淋巴细胞耗竭,也不需要进行传统 CAR T 细胞制备的β过程,这可能使 CAR 治疗更简单、更经济。它可以以按需和多样化治疗的形式,为个体化治疗提供更复杂的选择。