Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis. (March 2017)

• Record Type: Journal Article
• Authors: Koh, Eunee; Lee, Eun Jung; Nam, Gi-Hoon; Hong, Yeonsun; Cho, Eunji; Yang, Yoosoo; Kim, In-San
• Is Part Of: Biomaterials. Volume 121(2017)
• Page Start: 121
• Page End: 129
• Publication Date: 2017-03
• Subjects: Exosome -- Cancer immunotherapy -- CD47 -- Signal regulatory protein α -- Phagocytosis; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.01.004
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: CD47, a "don't eat me" signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRPα-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRPα proteins could effectively lead to phagocytic elimination of tumor cells both in vitro and in vivo . Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics.