Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Cancer Immunol Immunother. 2023 Nov;72(11):3739-3753. doi: 10.1007/s00262-023-03526-z. Epub 2023 Sep 14.
CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b CD19 lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b CD19 lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells.
嵌合抗原受体 T（CAR-T）细胞免疫疗法在复发性和难治性淋巴瘤治疗中实现了约 70%的缓解率。然而，淋巴瘤细胞表面 CD19 抗原的丢失或减少导致肿瘤细胞逃避 CD19 CAR-T 细胞（CAR19-T）的免疫杀伤。因此，迫切需要新的治疗策略。在这项研究中，构建了一种抗 CD79b/CD3 双特异性抗体（BV28-OKT3），并将其与 CAR19-T 细胞联合用于 B 细胞淋巴瘤治疗。当 CD19 抗原丢失或减少时，BV28-OKT3 将 CAR19-T 细胞重新导向 CD79b CD19 淋巴瘤细胞；因此，BV28-OKT3 通过 CAR19-T 细胞在体外和体内的杀伤作用克服了 CD79b CD19 淋巴瘤细胞的逃逸。此外，BV28-OKT3 触发了输注产品中 CAR T 细胞的抗肿瘤功能，并增强了旁观者 T 细胞的抗肿瘤免疫反应，显著提高了 CAR19-T 细胞对淋巴瘤细胞的体外和体内细胞毒性。此外，BV28-OKT3 在体外引发了供体来源的 T 细胞对淋巴瘤细胞的细胞毒性，这取决于肿瘤细胞的存在。因此，我们的研究结果为复发性和难治性 B 细胞淋巴瘤的治疗提供了一种新的临床治疗策略，即将 CD79b/CD3 BsAb 与 CAR19-T 细胞联合使用。
