Abstract A67: CD40 agonism inhibits tumor growth in murine hormone receptor positive breast cancer via CD8 T cells


 Breast cancer is the second most common malignancy affecting women and accounts for 15% of cancer-related mortality globally. Over 70% of breast cancers are hormone receptor (HR) positive (estrogen receptor and/or progesterone receptor positive) and human epidermal growth factor receptor 2 negative (HER2-). HR+HER2- breast cancers are poorly responsive to chemotherapy and recurrence and mortality remain high for patients with locally advanced disease. Thus, more therapeutic strategies are needed. Dendritic cell (DC) activation is an important pathway for T cell priming and subsequent improvements in immunosurveillance. In this study, we determined the ability of DC-targeted therapy with agonistic CD40 antibody to restore anti-tumor immunologic function in a murine orthotopic HR+HER2- breast cancer model. The Brpkp110 cell line was injected orthotopically into the abdominal mammary glands of 8 to 10-week-old C57BL/6 mice. Tumor-bearing mice treated with agonistic CD40 antibody (FGK4.5, 100 ug intraperitoneal) demonstrated decreased tumor growth and increased intratumoral CD8 T cells at 2 weeks. Both intratumoral DCs and tumor-associated macrophages in mice treated with agonistic CD40 were found to upregulate PD-L1 and CD40. CD8 T cell depletion abrogated the anti-tumor effect of agonistic CD40. Our data suggest that agonistic CD40 therapy may be a viable strategy for tumor inhibition and activation of anti-tumor immunity in HR+HER2- breast cancer.
 Citation Format: Jennifer Zhang, Olivia Lanchoney, Nikhil Joshi, Nune Markosyan, Robert Vonderheide. CD40 agonism inhibits tumor growth in murine hormone receptor positive breast cancer via CD8 T cells [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A67.