Zou Jianxuan, Chen Dan, Zong Yunhui, Ye Sisi, Tang Jinle, Meng Huimin, An Gangli, Zhang Xingding, Yang Lin
The Cyrus Tang Hematology Center, Soochow University, Suzhou, China.
Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Cancer Sci. 2015 May;106(5):512-21. doi: 10.1111/cas.12631. Epub 2015 Mar 13.
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.
双特异性抗体在免疫治疗中发挥着重要作用。它们受到了制药企业的强烈关注。首个抗体药物OKT3（鼠抗人CD3单克隆抗体）在临床治疗中表现出色。我们成功开发了一种抗CD3单链可变片段（ScFv）与抗CD138 ScFv结合并带有hIgG1 Fc（hIgFc）序列的产品。新型双特异性T细胞衔接器（BiTE）附加hIgFc（BiTE-hIgFc，STL001）可靶向T细胞、自然杀伤细胞和多发性骨髓瘤细胞（RPMI-8226或U266）。此外，BiTE-hIgFc（STL001）对重组人CD138蛋白具有纳摩尔级亲和力，并且在体外或体内对RPMI-8226细胞显示出比单独的aCD3-ScFv-hIgFc和aCD138-ScFv-hIgFc或同型单克隆抗体更强的抗肿瘤活性。
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