决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody.
Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody.
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。
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。
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.
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