A novel therapy for melanoma developed in mice: transformation of melanoma into dendritic cells with Listeria monocytogenes

PLoS One. 2015 Mar 11;10(3):e0117923. doi: 10.1371/journal.pone.0117923. eCollection 2015.

Abstract

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CHO Cells
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cricetulus
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Humans
  • Listeria monocytogenes / immunology*
  • Listeria monocytogenes / physiology
  • Melanoma / immunology
  • Melanoma / microbiology
  • Melanoma / therapy*
  • Mice
  • Neoplasm Transplantation
  • Skin Neoplasms / immunology
  • Skin Neoplasms / microbiology
  • Skin Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Tropism

Substances

  • Cancer Vaccines

Grants and funding

This work was supported by grants SAF2009-08695 and SAF2012-34203. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.