Tumor lysate particle loaded dendritic cell vaccine: preclinical testing of a novel personalized cancer vaccine

Immunotherapy. 2018 Apr;10(5):373-382. doi: 10.2217/imt-2017-0114.

Abstract

Aim: We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP).

Materials and methods: Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading. The in vivo effectiveness of tumor lysate (TL) particle loaded DC (TLPLDC) vaccine was assessed using murine melanoma models.

Results: In fluorescence-tagged experiments, YCWP efficiently delivered antigen to the cytoplasm of DC. TLPLDC loading was more effective than conventional exogenous loading of DC. Finally, in murine melanoma models, TLPLDC outperformed an analogous dendritoma vaccine.

Conclusion: The TLPLDC vaccine is commercially scalable and holds the potential of producing personalized vaccines.

Keywords: dendritic cell; immunotherapy; solid tumor; vaccine.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Immunotherapy / methods
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines