Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.
Institute of Molecular and Cellular Biology of the SB RAS, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 Feb 12;24(4):3698. doi: 10.3390/ijms24043698.
Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved by the FDA. Despite the spectacular rates of complete remission in r/r ALL and NHL patients, a significant proportion of patients still relapse, frequently with the CD19 low/negative tumor phenotype. To address this issue, additional B cell surface molecules such as CD20 were proposed as targets for CAR T cells. Here, we performed a side-by-side comparison of the activity of CD20-specific CAR T cells based on the antigen-recognition modules derived from the murine antibodies, 1F5 and Leu16, and from the human antibody, 2F2. Whereas CD20-specific CAR T cells differed from CD19-specific CAR T cells in terms of subpopulation composition and cytokine secretion, they displayed similar in vitro and in vivo potency.
在过去的十年中，嵌合抗原受体 T 细胞（CAR T）疗法已从一种实验性技术发展为一种临床可行的选择，用于治疗 B 细胞恶性肿瘤患者。迄今为止，已有四种针对 B 细胞表面标志物 CD19 的 CAR T 细胞产品获得美国食品药品监督管理局（FDA）的批准。尽管复发/难治性急性淋巴细胞白血病（ALL）和非霍奇金淋巴瘤（NHL）患者的完全缓解率很高，但仍有相当一部分患者会复发，且常伴有 CD19 低/阴性肿瘤表型。为了解决这个问题，人们提出了其他 B 细胞表面分子作为 CAR T 细胞的靶点，如 CD20。在此，我们基于源自鼠源抗体 1F5 和 Leu16 以及人源抗体 2F2 的抗原识别模块，对 CD20 特异性 CAR T 细胞的活性进行了并列比较。虽然 CD20 特异性 CAR T 细胞在亚群组成和细胞因子分泌方面与 CD19 特异性 CAR T 细胞不同，但它们在体外和体内的效力相似。
