A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response.

ABSTRACT: As a major immune cell type in the tumor microenvironment, tumor-associated macrophages secrete suppressive factors that can inhibit antitumor immunity and promote tumor progression. One approach trying to utilize macrophages for immunotherapy has been to block the CD47-SIRPα axis, which mediates inhibitory signaling, to promote phagocytosis of tumor cells. Many CD47-targeted agents, namely, anti-CD47 antibodies and SIRPα fusion proteins, were associated with a diverse spectrum of toxicities that limit their use in clinical settings. Universal expression of CD47 also leads to a severe "antigen sink" effect of CD47-targeted agents. Given that the CD47 receptor, SIRPα, has a more restricted expression profile and may have CD47-independent functions, targeting SIRPα is considered to have dist

SUBMITTER: Niu X 

PROVIDER: S-EPMC11384143 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature