title: Targeting CD47: the achievements and concerns of current studies on cancer immunotherapy.
abstract: Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction. This problem can be addressed by alternative animal models for better recapitulation of human CD47-SIRPα interaction. Both fragment crystallizable (Fc) fragment-dependent effects, like antibody-dependent cell-mediated cytotoxicity (ADCC), and Fc-independent CD47 intrinsic functions are involved in anti-CD47 therapy. The latter may be SIRPα-dependent or SIRPα-independent, such as the case of calreticulin. It has not reached a consensus which of the factors predominate the process, but the answer to this question will determine the optimal pharmaceutical and clinical design of CD47 targeting strategies.
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300071, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: University of the District of Columbia, Washington D.C., USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300071, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
keywords: CD47; antibody-dependent cell-mediated cytotoxicity (ADCC); calreticulin; syngeneic; xenograft