Abstract B058: VEGF inhibition enhances immune checkpoint blockade efficacy in ovarian cancer

Abstract In ovarian cancer, the efficacy of immune checkpoint inhibitors has been unsatisfactory. This failure has been attributed to the immune suppressive tumor microenvironment (TME) and restriction of T cell entry and activity within tumors. Vascular endothelial growth factor (VEGF) stimulates the polarization of M2 macrophages and supports stroma accumulation, thereby inhibiting T cell entry and function. This study aims to investigate whether pre-treatment with bevacizumab, αVEGF therapy, can modulate the immunosuppressive TME and enhance the efficacy of dual immune checkpoint blockade (ICB) in drug-resistant epithelial ovarian cancer (EOC). Across three humanized patient-derived xenograft (PDX) models, infused with patient-matched tumor-infiltrating lymphocytes (TILs) expanded ex vivo, bevacizumab pre-treatment followed by combined nivolumab (programmed cell death protein 1 inhibitor) and ipilimumab (cytotoxic T-lymphocyte-associated protein 4 blockade) resulted in the greatest increase survival compared to control treated animals. Flow cytometry and immunohistochemistry analyses demonstrated that T cells persisted in vivo for up to 13 weeks, with higher activity observed in the combination therapy groups. Additional ex vivo studies using ascites and ovarian tumor slice cultures show enhanced T cell effector function and increased macrophage related immunosuppression in response to monotherapy ICB and enhance tumor killing with the combination therapy. These findings provide new, unpublished evidence that bevacizumab pre-treatment can favorably alter the TME, thereby potentiating the anti-tumor activity of dual ICB in humanized models of drug-resistant EOC. We conclude that strategic modulation of the TME with bevacizumab prior to T cell-stimulating therapies may represent a promising approach to improve immunotherapy outcomes in ovarian cancer. Citation Format: Sai Preethi Nakkina, Sergey Medvedev, Kristy Ma, Matthew Anderson, Fiona Simpkins, Daniel Powell, Sarah Gitto. VEGF inhibition enhances immune checkpoint blockade efficacy in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B058.