Article
作者: Liegel, Jessica ; Muthuswamy, Senthil K ; Kufe, Donald ; Torres, Daniela ; Stroopinsky, Dina ; Hidalgo, Manuel ; Tacettin, Cansu ; Cheloni, Giulia ; Huang, Ling ; Ephraim, Adam ; Gandarilla, Omar ; Avigan, David ; Orr, Shira ; Rosenblatt, Jacalyn ; DeCicco, Cori ; Moser, James
BACKGROUNDPancreatic 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.RESULTSIn 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.CONCLUSIONSDC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.
