Huo Jianxin, Huang Yuhan, Zheng Ziying, Tay Xin Ni, Mahfut Farouq Bin, Zhang Wei, Lam Kong-Peng, Yang Yuansheng, Xu Shengli
Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore.
Bioprocessing Technology Institute, Agency for Science, Technology and Research, 20 Biopolis Way, Centros Building, Singapore 138668, Singapore.
Antib Ther. 2022 Jun 9;5(2):138-149. doi: 10.1093/abt/tbac012. eCollection 2022 Apr.
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 and .
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 . Using a MM xenograft mouse model, we demonstrate that the bsAb can effectively suppress MM cell growth .
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.
多发性骨髓瘤（MM）是第二常见的血液系统恶性肿瘤。它已成为下一个可能适合免疫治疗的血液系统疾病之一。B细胞成熟抗原（BCMA）是肿瘤坏死因子受体超家族的成员，在MM细胞中高表达，是开发针对MM的免疫治疗最具潜力的靶点之一。除了美国食品药品监督管理局（FDA）批准的靶向BCMA的嵌合抗原受体（CAR）T细胞疗法，如Abecma和CARVYKTI，T细胞接合多特异性抗体是另一种有前景的靶向BCMA治疗MM的治疗方式。我们开发了一种重定向T细胞的靶向BCMA双特异性抗体（bsAb）并评估其抗MM活性。
我们首先使用DNA免疫法产生了几种小鼠抗人BCMA单克隆抗体的克隆。然后使用其中一种抗BCMA抗体在CHO细胞中设计并生产了一种重定向T细胞的BCMA×CD3 bsAb。最后，我们检测了bsAb对MM细胞生长的影响。
BCMA×CD3 bsAb采用FabscFv形式设计，并在CHO细胞中产生，产量和纯度良好。此外，bsAb可触发强劲的T细胞增殖和激活，并诱导有效的T细胞介导的MM细胞杀伤。使用MM异种移植小鼠模型，我们证明bsAb可有效抑制MM细胞生长。
我们的结果表明，FabscFv形式的BCMA×CD3 bsAb可有效抑制MM细胞生长，具有开发成为治疗MM的治疗性抗体药物的潜力。
