A Novel Cancer Vaccine Strategy Based on HLA-A*0201 Matched Allogeneic Plasmacytoid Dendritic Cells

PLoS One. 2010 May 4;5(5):e10458. doi: 10.1371/journal.pone.0010458.

Abstract

Background: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy.

Methods and findings: Stimulation of PBMC from HLA-A*0201(+) donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+) CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment.

Conclusions: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Disease Progression
  • Epitopes / immunology
  • HLA-A Antigens / immunology*
  • HLA-A2 Antigen
  • Health
  • Histocompatibility Testing*
  • Humans
  • Melanoma / immunology*
  • Melanoma / pathology
  • Mice
  • Neoplasm Staging
  • Peptides / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tissue Donors
  • Vaccination

Substances

  • Cancer Vaccines
  • Epitopes
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Peptides