Golubovskaya Vita, Zhou Hua, Li Feng, Berahovich Robert, Sun Jinying, Valentine Michael, Xu Shirley, Harto Hizkia, Sienkiewicz John, Huang Yanwei, Wu Lijun
Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA.
Biology and Environmental Science College, Hunan University of Arts and Science, Changde 415000, China.
Biomedicines. 2021 Oct 9;9(10):1422. doi: 10.3390/biomedicines9101422.
Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target multiple myeloma. We generated a new CS1 (CD319, SLAM-7) antibody, clone (7A8D5), which specifically recognized the CS1 antigen, and we applied it for the generation of CS1-CAR. CS1-CAR-T cells caused specific killing of CHO-CS1 target cells with secretion of IFN-gamma and targeted multiple myeloma cells. In addition, bispecific CS1-BCMA-41BB-CD3 CAR-T cells effectively killed CHO-CS1 and CHO-BCMA target cells, killed CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma. Moreover, CS1-CAR-T cells and bispecific CS1-BCMA CAR-T cells effectively blocked MM1S multiple myeloma tumor growth in vivo. These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future clinical trials.
多发性骨髓瘤（MM）是一种由骨髓中浆细胞异常增殖引起的血液系统癌症，这种致命疾病需要新型治疗方法。在本研究中，我们旨在开发新型CS1嵌合抗原受体T细胞（CAR-T细胞）和双特异性CS1-BCMA CAR-T细胞，以特异性靶向多发性骨髓瘤。我们制备了一种新的CS1（CD319，信号淋巴细胞激活分子家族成员7）抗体，克隆号为（7A8D5），其能特异性识别CS1抗原，并将其应用于CS1-CAR的制备。CS1-CAR-T细胞通过分泌γ干扰素对CHO-CS1靶细胞产生特异性杀伤作用，并靶向多发性骨髓瘤细胞。此外，双特异性CS1-BCMA-41BB-CD3 CAR-T细胞能有效杀伤CHO-CS1和CHO-BCMA靶细胞，杀死CS1/BCMA阳性的多发性骨髓瘤细胞，并分泌γ干扰素。而且，CS1-CAR-T细胞和双特异性CS1-BCMA CAR-T细胞在体内能有效阻断MM1S多发性骨髓瘤肿瘤的生长。这些数据首次证明新型CS1和双特异性CS1-BCMA CAR-T细胞在靶向MM细胞方面是有效的，并为未来的临床试验提供了依据。
