Journal
BIOTECHNOLOGY LETTERS
Volume 40, Issue 5, Pages 789-795Publisher
SPRINGER
DOI: 10.1007/s10529-018-2535-2
Keywords
Bispecific antibody fusion protein; CD47; EGFR; Phagocytosis; Therapeutic index
Categories
Funding
- 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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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.
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