A novel bispecific antibody fusion protein co-targeting EGFR and CD47 with enhanced therapeutic index

作者：Yang, Yun; Guo, Rui; Chen, Qi; Liu, Youxun; Zhang, Pengfei; Zhang, Ziheng; Chen, Xi; Wang, Tianyun^*

来源：Biotechnology Letters, 2018, 40(5): 789-795.

DOI：10.1007/s10529-018-2535-2

• Bispecific antibody fusion protein
• CD47
• EGFR
• Phagocytosis
• Therapeutic index

To promote targeting specificity of anti-CD47 agents, we have constructed a novel bispecific antibody fusion protein against EGFR and CD47, which may minimize the "off-target" effects caused by CD47 expression on red blood cells. @@@ The novel bispecific antibody fusion protein, denoted as Bi-SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis-stimulation effects in vitro. Bi-SP treatment with a low dose more effectively inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRP alpha variant-Fc (SIRP alpha V-Fc) in the A431 xenograft tumor model. In addition, the treatment with Bi-SP produced less red blood cell (RBC) losses than the SIRP alpha V-Fc treatment, suggesting its potential use for minimizing RBC toxicity in therapy. @@@ Bi-SP with improved therapeutic index has the potential to treat CD47+ and EGFR+ cancers in clinics.

• 出版日期2018-5
• 单位新乡医学院; 浙江大学