一种新型双特异性抗体融合蛋白，共靶向表皮生长因子受体（EGFR）和信号调节蛋白α（CD47），具有更高的治疗指数。
A novel bispecific antibody fusion protein co-targeting EGFR and CD47 with enhanced therapeutic index.
作者信息
Yang Yun, Guo Rui, Chen Qi, Liu Youxun, Zhang Pengfei, Zhang Ziheng, Chen Xi, Wang Tianyun
机构信息
School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453000, Henan, People's Republic of China.
College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China.
出版信息
Biotechnol Lett. 2018 May;40(5):789-795. doi: 10.1007/s10529-018-2535-2. Epub 2018 Mar 29.
OBJECTIVE
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.
RESULTS
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 SIRPα variant-Fc (SIRPαV-Fc) in the A431 xenograft tumor model. In addition, the treatment with Bi-SP produced less red blood cell (RBC) losses than the SIRPαV-Fc treatment, suggesting its potential use for minimizing RBC toxicity in therapy.
CONCLUSIONS
Bi-SP with improved therapeutic index has the potential to treat CD47+ and EGFR+ cancers in clinics.
目的
为提高抗CD47药物的靶向特异性，我们构建了一种新型的抗表皮生长因子受体（EGFR）和CD47的双特异性抗体融合蛋白，这可能会将红细胞上CD47表达引起的“脱靶”效应降至最低。
结果
这种新型双特异性抗体融合蛋白，命名为Bi-SP，能够同时结合EGFR和CD47，并在体外表现出强大的吞噬刺激作用。在A431异种移植瘤模型中，低剂量的Bi-SP治疗比靶向EGFR的抗体Pan或信号调节蛋白α变体-Fc（SIRPαV-Fc）更有效地抑制肿瘤生长。此外，与SIRPαV-Fc治疗相比，Bi-SP治疗导致的红细胞（RBC）损失更少，表明其在治疗中具有将RBC毒性降至最低的潜在用途。
结论
具有改善治疗指数的Bi-SP有潜力在临床上治疗CD47+和EGFR+癌症。
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