Priming and activation of human ovarian and breast cancer-specific CD8+ T cells by polyvalent Listeria monocytogenes-based vaccines

J Immunother. 2009 Oct;32(8):856-69. doi: 10.1097/CJI.0b013e3181b0b125.

Abstract

Immunotherapeutic vaccine is potentially an effective strategy to combat cancer. Essential components of an effective vaccine must include antigens that are processed by the major histocompatibility complex class I pathway, presented by the tumor major histocompatibility complex molecules, and an effective antigen delivery platform that is capable of breaking self-tolerance. In this study, we characterized a set of ovarian cancer-specific T-cell epitopes delivered by live-attenuated recombinant Listeria monocytogenes (Lm DeltaactADeltainlB) as a vaccine vector. We present data that peptide-specific T cells recognize the human monocytic cell line THP-1 infected with recombinant Lm DeltaactADeltainlB encoding the epitopes. Furthermore, we demonstrate that recombinant L. monocytogenes (Lm)-infected antigen-presenting cells can prime and expand epitope-specific CD8 T cells in vitro and such CD8 T cells recognize not only peptide-loaded targets but also ovarian and breast tumor cells presenting endogenous epitopes. Finally, peptide-specific T cells generated using peripheral blood mononuclear cell from ovarian cancer patients recognize target cells infected with recombinant Lm DeltaactADeltainlB encoding the epitopes. Our results demonstrate that live-attenuated recombinant Lm can be used effectively as a vehicle to deliver cancer peptide antigens singly or as a multiepitope construct. Thus, the use of recombinant live-attenuated Lm strains encoding endogenously processed and presented tumor epitopes/antigens represents an attractive strategy for active cancer immunotherapy in a clinical setting.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • HLA-A2 Antigen / metabolism
  • Humans
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology
  • Lymphocyte Activation
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / microbiology
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen