Anti-CD19 chimeric antigen receptor (CAR)-engineered T and NK cell therapies have revolutionized the treatment of B cell malignancies, but challenges including CD19 antigen loss greatly hinder their full therapeutic potential. Here we demonstrated that co-treatment with anti-CD19 monoclonal antibody enhances antitumor activity of anti-CD19 CAR-T and -NK cells. Even though the treated antibody interferes with CD19 antigen binding of CAR, it significantly induces rapid detachment of anti-CD19 CAR effector cells from target cells, facilitating improved serial killing. This reduced interaction between CAR effector cells and target cells also leads to the alleviation of CAR-mediated trogocytosis. Interestingly, co-treatment with anti-CD19 antibody reveals time-dependent effects on the antitumor activity of anti-CD19 CAR-T cells, characterized by a reduction in early T cell activation followed by sustained high activity during prolonged exposure to target cells. This temporal modulation ultimately results in enhanced antitumor potency in vivo. These findings underscore the improved therapeutic efficacy achieved by combining anti-CD19 antibody with anti-CD19 CAR-T or -NK cells against B cell malignancies.

中文翻译：

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抗 CD19 抗体共处理可增强抗 CD19 CAR-T/-NK 细胞的连续杀伤活性并减少胞吞作用。


抗 CD19 嵌合抗原受体 （CAR） 工程改造的 T 细胞和 NK 细胞疗法彻底改变了 B 细胞恶性肿瘤的治疗，但包括 CD19 抗原缺失在内的挑战极大地阻碍了其全部治疗潜力。在这里，我们证明与抗 CD19 单克隆抗体的共同处理增强了抗 CD19 CAR-T 和 -NK 细胞的抗肿瘤活性。尽管处理后的抗体会干扰 CAR 的 CD19 抗原结合，但它会显著诱导抗 CD19 CAR 效应细胞与靶细胞的快速分离，从而促进改善连续杀伤。CAR 效应细胞和靶细胞之间相互作用的减少也导致 CAR 介导的胞胎作用的缓解。有趣的是，与抗 CD19 抗体的共同处理揭示了对抗 CD19 CAR-T 细胞抗肿瘤活性的时间依赖性影响，其特征是早期 T 细胞活化减少，随后在长时间暴露于靶细胞期间保持高活性。这种时间调节最终导致体内抗肿瘤效力增强。这些发现强调了抗 CD19 抗体与抗 CD19 CAR-T 或 -NK 细胞联合治疗 B 细胞恶性肿瘤所实现的治疗效果的提高。