Abstract A106: Synergistic Effects of CD40 Agonist Antibody and DC-Derived Exosomes Enhance Anti-Tumor Efficacy by Modulating the Tumor Microenvironment and Reducing Metastasis in a Murine Melanoma Model

Abstract Over the past decade, dendritic cell (DC) vaccines have been extensively studied to reprogram the tumor microenvironment (TME) and delay tumor growth. However, limitations related to long-term storage, patient- specific variability, short half-life, and moderate anti-tumor efficacy highlight the need for further refinement of DC vaccines for effective cancer treatment. As an alternative, DC-derived exosomes (DeX) have demonstrated superior anti-tumor efficacy and stability compared to DCs. However, within tumors, low expression of co- stimulatory molecules such as CD40, CD86, and CD80 limits the effectiveness of these cancer vaccines. The use of a CD40 agonist antibody (αCD40) has shown potential in increasing CD40 expression, enhancing antigen presentation, and contributing to a robust anti-tumor response. In this study, we demonstrate that combining αCD40 with DeX pulsed with cancer cell lysate significantly delayed tumor growth and improved survival in mice bearing B16-F10 melanoma. In tumor, the combination therapy increased the population of CD45+CD8+ T-cells and CD45+CD20+ B-cells, while reducing PD-L1 expression. Additionally, the combination therapy boosted levels of Th1 cytokines (IFN-γ, IL-6, IL-2) compared to Th2 cytokines (IL-4 and IL-10), supporting an enhanced anti-tumor response. Importantly, this approach also augmented anti-tumor immunity in the spleen, significantly lowered the expression of metastatic markers including vimentin, and fibronectin in the primary tumor, and reduced lung metastasis. Overall, these findings suggest that the combined use of αCD40 and DeX is a promising strategy to improve the in vivo anti-tumor efficacy of DC vaccines and supports further exploration of this novel combinatorial therapy in clinical settings. Citation Format: Vidit Gaur, Jayanta Bhattacharyya. Synergistic Effects of CD40 Agonist Antibody and DC-Derived Exosomes Enhance Anti-Tumor Efficacy by Modulating the Tumor Microenvironment and Reducing Metastasis in a Murine Melanoma Model [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 A106.