Abstract 3471: CD47 blockade-based local immunotherapy for endometrial cancer

Abstract Endometrial cancer (EC) incidence and mortality have been persistently increasing, indicating the limitations of current therapeutic measures. We have developed an immunotherapy for EC targeting the immune checkpoint molecule CD47. CD47 is a transmembrane protein that serves as a ligand for receptor signal regulatory protein-α (SIRPα) expressed on macrophages. When CD47 on tumor cells and SIRPα on macrophages interact, phagocytosis of malignant cells is inhibited. We found that macrophage phagocytosis of human EC cells is enhanced by an anti-CD47 monoclonal antibody (mAb). Our preclinical studies revealed the anti-CD47 mAb effectively reduces tumor burden without displaying overt signs of toxicity when administered through transvaginal local treatment in PR-cre+/-;Ptenflox/flox female mice with endometrial carcinoma. Thus, our findings provide rationale for the clinical application of anti-CD47 local immunotherapy to benefit women at risk for endometrial cancer development. Citation Format: Kerem Yucebas, Sooah Ko, Omair Khan, Irving Weissman, Shiying Jin. CD47 blockade-based local immunotherapy for endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3471.