CD20 双特异性抗体可改善淋巴瘤体外和 CLL 体内模型中对 CD19-CAR T 细胞的反应。
CD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models.
发表日期：2024 May 28
作者：
Berit J Brinkmann, Alessia Floerchinger, Christina Schniederjohann, Tobias Roider, Mariana Coelho, Norman Mack, Peter-Martin Bruch, Nora Liebers, Sarah Dötsch, Dirk H Busch, Michael Schmitt, Frank Neumann, Philipp M Roessner, Martina Seiffert, Sascha Dietrich
来源：
BLOOD
摘要：
抗 CD19 嵌合抗原受体 T 细胞 (CD19-CAR) 是治疗复发/难治性 B 细胞恶性肿瘤的有效方法，但不完全反应通常会导致疾病早期进展。我们在此评估了联合施用 CD20 靶向双特异性抗体 (CD20-BsAb) 与 CD19-CAR 的潜在益处，旨在增强免疫治疗功效。将 CD20-BsAb 添加到 CD19-CAR 和 B 细胞恶性肿瘤原代样品（包括恶性 B 细胞和内源性 T 细胞）的共培养物中，显着改善了对恶性细胞的杀伤，同时增强了内源性 T 细胞和 CD19- 的扩增车。 CD20-BsAb 诱导内源性 T 细胞和 CD19-CAR 的增殖和激活增加。在免疫功能正常的 CLL 小鼠模型中，CD19-CAR 单一疗法后初次治疗反应后复发经常发生。与注射 CD20-BsAb 相结合可显着增强治疗反应并改善恶性细胞的根除。更高的疗效伴随着 CD20-BsAb 给药后 T 细胞扩增的改善，并导致更长的生存期，80% 的小鼠在治疗开始后八周内治愈，没有检测到恶性细胞群。总的来说，我们的体外和体内数据表明，当 CD19-CAR 与 CD20-BsAb 联合使用时，可增强 B 细胞恶性肿瘤的治疗效果。输注的 CAR T 细胞以及内源性 T 细胞的激活和增殖可能有助于改善疾病控制。版权所有 © 2024 美国血液学会。
Anti-CD19 chimeric antigen receptor T-cells (CD19-CAR) represent an effective treatment for relapsed/refractory B-cell malignancies but incomplete responses often result in early disease progression. We here assessed potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAb) with CD19-CAR, aiming to enhance immunotherapeutic efficacy. Addition of CD20-BsAb to co-cultures of CD19-CAR and primary samples of B-cell malignancies, comprising malignant B- and endogenous T-cells, significantly improved killing of malignant cells alongside enhanced expansion of both endogenous T-cells and CD19-CAR. CD20-BsAb induced an increase in proliferation and activation of endogenous T-cells and CD19-CAR. In an immunocompetent mouse model of CLL, relapse after initial treatment response frequently occurred after CD19-CAR monotherapy. Combination with injections of CD20-BsAb significantly enhanced treatment response and resulted in improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion upon CD20-BsAb administration and resulted in longer survival, with 80% of mice being cured with no detectable malignant cell population within eight weeks of therapy initiation. Collectively, our in-vitro and in-vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR when combined with CD20-BsAb in B-cell malignancies. Activation and proliferation of both infused CAR T-cells as well as endogenous T-cells may contribute to improved disease control.Copyright © 2024 American Society of Hematology.