Autologous versus allogeneic peptide-pulsed dendritic cells for anti-tumour vaccination: Expression of allogeneic MHC supports activation of antigen specific T cells, but impairs early naïve cytotoxic priming and anti-tumour therapy

Alison Merrick, Rosa Maria Diaz, Dearbhaile O'Donnell, Peter Selby, Richard Vile, Alan Melcher

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: Dendritic cells (DC) pulsed with MHC class I-restricted tumour associated antigen (TAA) peptides have been widely tested in pre-clinical models and early clinical studies for their ability to prime cytotoxic T cell (CTL) responses. The effect of co-expression of allogeneic MHC antigens on DC immunogenicity has not been addressed, and has implications for the feasibility of clinical applications. Objective: This study compared DC from autologous H-2b or semi-allogeneic F1 H-2bxk mice pulsed with the H-2b-restricted model ovalbumin (OVA) peptide SIINFEKL, and compared in vitro and in vivo their ability to (i) activate specific OT1 cells, (ii) prime naïve CTL, and (iii) protect against B16.OVA challenge. Peptide-pulsed autologous and allogeneic DC were also tested in naïve human CTL priming assays. Results: Semi-allogeneic DC expressed higher levels of co-stimulatory molecules. On pulsing with SIINFEKL they triggered greater proliferation of OT1 cells in vitro and in vivo, but were less effective at naïve CTL priming and tumour protection. Autologous human DC were similarly more potent at naïve CTL priming against the melanoma-associated TAA MART-1 in vitro. Conclusion: The expression of allogeneic MHC antigens on peptide-pulsed DC impairs naïve CTL priming and anti-tumour effects, despite effective TAA presentation both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)897-906
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume57
Issue number6
DOIs
StatePublished - Jun 1 2008

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Keywords

  • Cancer immunotherapy
  • Cancer vaccines
  • Dendritic cells
  • Tumour-associated antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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