靶向 B 细胞成熟抗原、抑制多发性骨髓瘤细胞生长的 T 细胞重定向双特异性抗体的开发

Multiple myeloma (MM) is the second most common hematological malignancy. It has emerged as one of the next possible hematological diseases amenable to immunotherapy. B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is highly expressed in MM cells and is one target with the most potential for developing MM-targeting immunotherapy. Other than the FDA-approved BCMA-targeting CAR T-cell therapy, such as Abecma and CARVYKTI, T cell-engaging multi-specific antibody is another promising therapeutic modality for BCMA-targeting MM treatment. We develop a T-cell redirecting BCMA-targeting bispecific antibody (bsAb) and evaluate its anti-MM activity.

We first generated several clones of mouse anti-human BCMA monoclonal antibodies using DNA immunization. One of the anti-BCMA antibodies was then used to design and produce a T cell-redirecting BCMA CD3 bsAb in CHO cells. Finally, we examined the effect of the bsAb on MM cell growth both in vitro and in vivo .

The BCMA CD3 bsAb was designed in a FabscFv format and produced in CHO cells with good yield and purity. Moreover, the bsAb can trigger robust T cell proliferation and activation and induce efficient T cell-mediated MM cell killing in vitro . Using a MM xenograft mouse model, we demonstrate that the bsAb can effectively suppress MM cell growth in vivo .

Our results suggest that the BCMA CD3 bsAb in the FabscFv format can efficiently inhibit MM cell growth and have promising potential to be developed into a therapeutic antibody drug for the treatment of MM.