Orr et al. examined the capacity of DC/tumor cell fusions to induce immune responses against pancreatic cancer cells. Compared to unvaccinated controls, mice vaccinated with a fusion of KPC cells (isolated from spontaneous pancreatic tumors) and bone marrow-derived DCs had slower tumor growth, improved survival time, and increased tumor recognition by T cells upon post-euthanasia ex vivo stimulation. In the PAN02 pancreatic cancer model, tumor/DC fusions elicited specific tumor immunity in vitro and in vivo. Patient-derived autologous DC/tumor fusions induced tumor-specific CD4+ and CD8+ activation upon ex vivo stimulation.
Contributed by Margot O’Toole
BACKGROUND: Pancreatic cancer is a highly lethal malignancy often presenting with advanced disease and characterized by resistance to standard chemotherapy. Immune-based therapies such checkpoint inhibition have been largely ineffective such that pancreatic cancer is categorized as an immunologically "cold tumor". In the present study, we examine the therapeutic efficacy of a personalized cancer vaccine in which tumor cells are fused with dendritic cells (DC) resulting in the broad induction of antitumor immunity. RESULTS: In the KPC spontaneous pancreatic cancer murine model, we demonstrated that vaccination with DC/KPC fusions led to expansion of pancreatic cancer specific lymphocytes with an activated phenotype. Remarkably, vaccination led to a reduction in tumor bulk and near doubling of median survival in this highly aggressive model. In a second murine pancreatic model (Panc02), vaccination with DC/tumor fusions similarly led to expansion of tumor antigen specific lymphocytes and their infiltration to the tumor site. Having shown efficacy in immunocompetent murine models, we subsequently demonstrated that DC/tumor fusions generated from primary human pancreatic cancer and autologous DCs potently stimulate tumor specific cytotoxic lymphocyte responses. CONCLUSIONS: DC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.