Abstract 3547: Therapeutic efficacy of genetically modified CD34-derived allogeneic dendritic cell cancer vaccine platform in a pancreatic tumor model

Abstract Background: Pancreatic cancer is the fourth leading cause of all cancer-related deaths. Dendritic cells are the primary antigen presenting cells that have the capacity to activate both innate and adaptive immune systems. Although peripheral blood derived mature dendritic cell (DC)-based vaccines have shown the potential to activate multiple anti-tumor immune responses in-vitro and in animal studies, they have yielded disappointing results in clinical trials. Here we report on a novel allogeneic dendritic cell cancer vaccine (DCCV) platform derived from CD34+ Hematopoietic Stem Cells (HSCs) that are transduced with lentiviral vector encoding CD93, CD40L, and CXCL13. We are reporting therapeutic efficacy of such allogeneic dendritic cell cancer vaccine therapy platform in a pancreatic tumor bearing humanized mouse model. Methods: We have developed a robust manufacturing method to generate large numbers of engineered allogenic DCs overexpressing CD93, CD40L, and CXCL13. A tri-cistronic lentiviral vector was constructed to co-express these genes. The engineered DCs were evaluated for the expression of transgenes and functionality via flow cytometry, PCR, and ELISA. Antigen education of engineered DCs was performed via coculturing them with whole tumor lysate. In vivo therapeutic efficacy was tested in Bone-Liver-Thymus (BLT) and PBMC humanized NOD-SCID gamma (NSG) mouse models with Mia Paca-2 (MP2) orthotopic pancreatic tumors. Chromium release assay, E-sight and IHC methods were employed to quantify the cytotoxicity and cell proliferation of T cells and infiltration of immune cells into the tumors upon treatment with the engineered DC. Results: We have investigated the therapeutic efficacy of our engineered DCCV in curtailing pancreatic tumor growth. Tumor-bearing Humanized mouse models treated with engineered DCCV demonstrated significant tumor regression compared to untreated controls. This is accredited to DCCV’s ability to activate the host immune system, proliferation of CD4+, CD8+, and NK cells in the peripheral blood and subsequent infiltration of these immune cells into the tumor tissue. Conclusion: These results demonstrate the potency of our allogeneic DCCV expressing CD93, CD40L, and CXCL13, in controlling pancreatic tumor growth by stimulating the immune system and therefore could provide an effective therapeutic opportunity for the treatment of various solid tumors. We report on a DCCV platform to treat multiple solid tumors such as triple negative breast cancer (TNBC), hepatocellular carcinoma, pancreatic, head and neck, oral and prostate cancers. Citation Format: Jose Dominic Gonzalez, Sara Huerta-Yepez, Neha Sheik, Senay Beraki, Elango Kathirvel, Ariel Rodriguez Frandsen, Saleemulla Mahammad, Lu Chen, Francois Binette, David Weinstein, Anahid Jewett. Therapeutic efficacy of genetically modified CD34-derived allogeneic dendritic cell cancer vaccine platform in a pancreatic tumor model [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 3547.