Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
Molecular Medicine Partnership Unit, Heidelberg, Germany.
Blood. 2024 Aug 15;144(7):784-789. doi: 10.1182/blood.2023022682.
Relapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.
抗 CD19 嵌合抗原受体 (CD19-CAR) 治疗后,相当一部分淋巴恶性肿瘤患者会出现疾病复发。我们评估了共给予 CD20 靶向双特异性抗体 (CD20-BsAb) 与 CD19-CAR T 细胞的潜在益处,旨在增强免疫治疗效果。将 CD20-BsAb 添加到 CD19-CAR 和 B 细胞恶性肿瘤的原代样本的共培养物中,显著改善了对恶性细胞的杀伤作用,并增强了内源性 T 细胞和 CD19-CAR T 细胞的扩增。在慢性淋巴细胞白血病的免疫功能正常的小鼠模型中,在初始治疗反应后,CD19-CAR T 细胞单药治疗后经常发生疾病复发。用 CD20-BsAb 进行额外治疗显著增强了治疗反应,并导致恶性细胞的清除得到改善。疗效提高伴随着 CD20-BsAb 给药时 T 细胞的扩增改善,并且在 8 周的治疗开始后,80%的小鼠被治愈,未检测到恶性细胞群,从而延长了生存时间。总之,我们的体外和体内数据表明,在 B 细胞恶性肿瘤中,CD19-CAR T 细胞与 CD20-BsAb 联合使用具有增强的治疗效果。输注的 CAR T 细胞和内源性 T 细胞的激活和增殖可能有助于改善疾病控制。
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