肿瘤细胞治疗研究
英文原题：Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis.
Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis.
抗 CD19 嵌合抗原受体（CAR）工程化的 T 细胞和自然杀伤（NK）细胞疗法彻底改变了 B 细胞恶性肿瘤的治疗，但包括 CD19 抗原丢失在内的挑战极大地阻碍了其充分发挥治疗潜力。
靶向CD19的嵌合抗原受体（CAR）工程化T细胞和自然杀伤（NK）细胞疗法改变了B细胞恶性肿瘤的治疗，但CD19抗原丢失等挑战严重限制其全部治疗潜力。本研究发现，联合使用抗CD19单克隆抗体可增强抗CD19 CAR-T和CAR-NK细胞的抗肿瘤活性。尽管抗体会干扰CAR对CD19抗原的结合，但其显著促进抗CD19 CAR效应细胞快速脱离靶细胞，从而改善连续杀伤能力。CAR效应细胞与靶细胞相互作用减少，也降低了CAR介导的抗原啃噬（trogocytosis）。有趣的是，联合抗CD19抗体对CAR-T细胞抗肿瘤活性的影响具有时间依赖性：早期T细胞活化降低，随后在长时间接触靶细胞时保持较高活性。这种时间调节最终增强了体内抗肿瘤效力。这些发现强调，抗CD19抗体与抗CD19 CAR-T或CAR-NK细胞联合可提高其治疗B细胞恶性肿瘤的疗效。
Anti-CD19 chimeric antigen receptor (CAR)-engineered T and natural killer (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 revealed that cotreatment 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, cotreatment 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.
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