A novel bispecific antibody fusion protein co-targeting EGFR and CD47 with enhanced therapeutic index
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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 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.
Bi-SP with improved therapeutic index has the potential to treat CD47+ and EGFR+ cancers in clinics.
KeywordsBispecific antibody fusion protein CD47 EGFR Phagocytosis Therapeutic index
We thank Binfeng Cheng, Huaizu Guo and Jin Xu for their expert technical assistance. This work was supported by grants from the Natural Science Foundation of China (81703054, 81403161, 21605074), National Training Program of Innovation for Undergraduates (201710472029), Key scientific research project of higher education of Henan Province, China (17A350012), Key Science and Technology Program of Henan Province, China (172102310614), Doctoral Foundation of Xinxiang Medical University (XYBSKYZZ201506).
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