Abstract A103: Local immunotherapy for endometrial cancer via CD47 blockade

Abstract A persistent increase in endometrial cancer incidence and mortality reflects the limitations of current therapeutic measures. In this study, we developed a local immunotherapy targeting the immune checkpoint molecule, CD47, which utilizes tissue resident macrophages for the elimination of endometrial cancer (EC). CD47 is a transmembrane protein that serves as a ligand for receptor signal regulatory protein-α (SIRPα) expressed on macrophages. The interaction between CD47 on malignant cells and SIRPa on macrophages inhibits phagocytosis of tumor cells. Our data reveals a high density of tumor-associated macrophages (TAMs) within the human endometrial cancer microenvironment, and that human EC cells upregulate their surface CD47 expression. In vitro functional assay shows that the anti-CD47 monoclonal antibody (mAb) enhances the phagocytosis of human EC cells by macrophages. Both systemic treatment via intraperitoneal injection and local treatment via transvaginal administration with the anti-CD47 mAb effectively reduces tumor burden in vivo in PR-cre +/- ;Pten flox/flox female mice, a genetically engineered mouse model of endometrial cancer. Further efficacy comparison reveals that the local anti-CD47 mAb treatment results in improved outcomes without displaying overt signs of adverse effects. In current practice, transvaginal delivery of treatments for gynecological conditions is used extensively. Thus, local treatment via transvaginal administration of anti-CD47 mAb to facilitate direct and maximal targeting of primary endometrial cancer cells is a feasible and promising avenue for the treatment of EC. Citation Format: Kerem Yucebas, Sooah Ko, Omair Khan, Irving Weissman, Shi-Ying Jin. Local immunotherapy for endometrial cancer via CD47 blockade [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A103.