Personalized tumor vaccine for pancreatic cancer

Cancer Immunol Immunother. 2023 Feb;72(2):301-313. doi: 10.1007/s00262-022-03237-x. Epub 2022 Jul 14.

Abstract

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.

Keywords: Cancer vaccines; Dendritic cells; Pancreatic cancer.

MeSH terms

  • Animals
  • Cancer Vaccines*
  • Dendritic Cells
  • Humans
  • Lymphocyte Activation
  • Mice
  • Pancreatic Neoplasms*

Substances

  • Cancer Vaccines