Yun Yang1, Rui Guo2, Qi Chen3, Youxun Liu1, Pengfei Zhang1, Ziheng Zhang1, Xi Chen3, Tianyun Wang4. 1. School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453000, Henan, People's Republic of China. 2. College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China. 3. Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 4. School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453000, Henan, People's Republic of China. wty@xxmu.edu.cn.
Abstract
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.
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.
Entities:
Keywords:
Bispecific antibody fusion protein; CD47; EGFR; Phagocytosis; Therapeutic index
Authors: Oscar Arrieta; Alejandro Aviles-Salas; Mario Orozco-Morales; Norma Hernández-Pedro; Andrés F Cardona; Luis Cabrera-Miranda; Pedro Barrios-Bernal; Giovanny Soca-Chafre; Graciela Cruz-Rico; María de Lourdes Peña-Torres; Guadalupe Moncada-Claudio; Laura-Alejandra Ramirez-Tirado Journal: Cancer Med Date: 2020-02-11 Impact factor: 4.452