← 返回前沿论文

采用重组抗 CD7 阻断抗体的新型抗 CD7 CAR-T 细胞制备策略的可行性研究

英文原题:Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody.

查看英文原题

Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody.

PubMed 2022/02/20(内容时间) Mol Ther Oncolytics

研究概要

尽管嵌合抗原受体(CAR)T细胞免疫疗法在B细胞恶性肿瘤中显示出重要意义,但由于正常T细胞与恶性T细胞之间存在共享抗原性,导致自相残杀并阻碍了用于临床治疗的CAR生产,因此针对T细胞恶性肿瘤的成功仍不理想。

中文摘要

尽管嵌合抗原受体(CAR)T细胞免疫疗法在B细胞恶性肿瘤中显示出良好前景,但其治疗T细胞恶性肿瘤的成功仍不理想,因为正常和恶性T细胞具有共同抗原性,导致CAR-T细胞发生同类相残,并阻碍临床治疗所需CAR-T细胞的生产。我们报告一种新策略:利用重组抗CD7抗体阻断T细胞表面的CD7抗原,从而获得足量靶向CD7的CAR-T细胞,用于治疗T细胞急性淋巴细胞白血病(T-ALL)。系统评估可行性后发现,抗体阻断CD7抗原可有效阻止CD7介导的同类相残、提高扩增率、降低调节性T(Treg)细胞比例、维持T细胞干细胞样特征,并恢复CD8+ T细胞群比例。最终,我们获得了可特异性且有效杀伤CD7抗原阳性靶细胞的抗CD7 CAR-T细胞,无需复杂的T细胞改造。该方法比既往方法更安全,为靶向CD7阳性恶性肿瘤的临床免疫治疗提供了新的、简便可行的策略。

展开英文摘要原文

Although chimeric antigen receptor (CAR) T cell immunotherapy has shown promising significance in B cell malignancies, success against T cell malignancies remains unsatisfactory because of shared antigenicity between normal and malignant T cells, resulting in fratricide and hindering CAR production for clinical treatment. Here, we report a new strategy of blocking the CD7 antigen on the T cell surface with a recombinant anti-CD7 antibody to obtain a sufficient amount of CD7-targeting CAR-T cells for T cell acute lymphoblastic leukemia (T-ALL) treatment. Feasibility was evaluated systematically, revealing that blocking the CD7 antigen with an antibody effectively blocked CD7-derived fratricide, increased the expansion rate, reduced the proportion of regulatory T (Treg) cells, maintained the stem cell-like characteristics of T cells, and restored the proportion of the CD8 + T cell population. Ultimately, we obtained anti-CD7 CAR-T cells that were specifically and effectively able to kill CD7 antigen-positive target cells, obviating the need for complex T cell modifications. This approach is safer than previous methods and provides a new, simple, and feasible strategy for clinical immunotherapies targeting CD7-positive malignant tumors.

论文信息

作者
Ye J、Jia Y、Tuhin IJ、Tan J、Monty MA、Xu N、Kang L、Li M
单位
Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China.China
期刊
Molecular therapy oncolytics2022 Mar 17
原文标识
PubMed 35317521 · DOI 10.1016/j.omto.2022.02.013