Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar 15;9(381):eaaf2968.
doi: 10.1126/scitranslmed.aaf2968.

Disrupting the CD47-SIRPα Anti-Phagocytic Axis by a Humanized anti-CD47 Antibody Is an Efficacious Treatment for Malignant Pediatric Brain Tumors

Affiliations

Disrupting the CD47-SIRPα Anti-Phagocytic Axis by a Humanized anti-CD47 Antibody Is an Efficacious Treatment for Malignant Pediatric Brain Tumors

Sharareh Gholamin et al. Sci Transl Med. .

Abstract

Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic agent for managing multiple pediatric central nervous system malignancies.

Comment in

Similar articles

See all similar articles

Cited by 49 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback