CD20-selective inhibition of CD47-SIRPα "don't eat me" signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab. (1st February 2018)

• Record Type: Journal Article
• Authors: van Bommel, Peter E.; He, Yuan; Schepel, Ilona; Hendriks, Mark A. J. M.; Wiersma, Valerie R.; van Ginkel, Robert J.; van Meerten, Tom; Ammatuna, Emanuele; Huls, Gerwin; Samplonius, Douwe F.; Helfrich, Wijnand; Bremer, Edwin
• Is Part Of: Oncoimmunology. Volume 7:Number 2(2018)
• Publication Date: 2018-02-01
• Subjects: bispecific antibody -- CD47 -- phagocytosis -- rituximab -- SIRPα; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1386361
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα "don't eat me" signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20 pos /CD47 pos malignant B-cells, but not of CD20 neg /CD47 pos cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer antibodies daratumumab (anti-CD38), alemtuzumab (anti-CD52) and obinutuzumab (anti-CD20). In conclusion, RTX-CD47 blocks CD47 "don't eat me" signaling by cancer cells in a CD20-directed manner with essentially no activity towards CD20 neg /CD47 pos cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies.