Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma

基于 hIgG1 Fc 序列双特异性 T 细胞接合剂的免疫疗法作为多发性骨髓瘤的新治疗策略

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作者:Jianxuan Zou, Dan Chen, Yunhui Zong, Sisi Ye, Jinle Tang, Huimin Meng, Gangli An, Xingding Zhang, Lin Yang

Abstract

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab-CD3), showed great performance in clinical treatment. We have successfully developed a single-chain variable fragment (ScFv) combination of anti-CD3 ScFv and anti-CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T-cell engager (BiTE) with an additional hIgFc (BiTE-hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI-8226 or U266). In addition, BiTE-hIgFc (STL001) has nanomolar-level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI-8226 cells than that of separate aCD3-ScFv-hIgFc and aCD138-ScFv-hIgFc, or the isotype mAb in vitro or in vivo.

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