分泌 IL-7 和 CCL21 的优化 BCMA/CS1 双特异性 TRuC-T 细胞有效控制多发性骨髓瘤

The bispecific TRuC-T cells simultaneously targeting B cell maturation antigen (BCMA) and CD2 subset 1 (CS1) were constructed by pairing two of five subunits (i.e., TCR C, TCR C, CD3 , CD3 , and CD3 ) in the TCR/CD3 complex and were named C-AC-B-3E, C-BC-B-3E, C-3G-B-3E, C-3D-B-3E, C-3E-B-3E, B-3E-C-3E, B-3G-C-3E, and B-3D-C-3E. Additionally, the BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21, named BC-7 21 TRuC-T cells, were generated. All of the bispecific TRuC-T cells were characterized and tested in vitro and in vivo .

Following the optimization of various pairs of two subunits of TCR/CD3 complex, B-3G-C-3E TRuC-T cells, characterized by incorporating CD3 and CD3 , exhibited the strongest myeloma-specific cytotoxicity. Furthermore, the bispecific BC-7 21 TRuC-T cells had stronger proliferation, chemotaxis, and cytotoxicity in vitro . Accordingly, the bispecific BC-7 21 TRuC-T cells showed better persistence in vivo so as to effectively suppress tumor growth in the NCG mouse xenograft model of MM.1S multiple myeloma. DISCUSSION: This study demonstrated that BC-7 21 TRuC-T cells, engineered through the optimization of the two subunits of TCR/CD3 complex and a co-expression cytokine strategy, may offer a novel and effective therapy for relapsed/refractory multiple myeloma.