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CD20 特异性 CAR T 细胞的比较临床前分析,包含基于 1F5、Leu16 和 2F2 的抗原识别结构域。

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties.

机构信息

Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.

Institute of Molecular and Cellular Biology of the SB RAS, 630090 Novosibirsk, Russia.

出版信息

Int J Mol Sci. 2023 Feb 12;24(4):3698. doi: 10.3390/ijms24043698.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/9966244/67321df22789/ijms-24-03698-g001.jpg

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