Dendritic cells engineered to express defined allo-HLA peptide complexes induce antigen-specific cytotoxic T cells efficiently killing tumour cells

Scand J Immunol. 2009 Apr;69(4):319-28. doi: 10.1111/j.1365-3083.2008.02223.x.


Most tumour-associated antigens (TAA) are non-mutated self-antigens. The peripheral T cell repertoire is devoid of high-avidity TAA-specific cytotoxic T lymphocytes (CTL) due to self-tolerance. As tolerance is major histocompatibility complex-restricted, T cells may be immunized against TAA presented by a non-self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo-restricted CTL of high-avidity and low cross-reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA-A*0201, efficiently present externally loaded peptides from the antigen, Melan-A/MART-1 to T cells from HLA-A*0201-negative donors. CD8(+) T cells binding HLA-A*0201/MART-1 pentamers were detected already after 12 days of co-culture in 11/11 donors. The majority of cells from pentamer(+) cell lines were CTL and efficiently killed HLA-A*0201(+) melanoma cells, whilst sparing HLA-A*0201(+) B-cells. Allo-restricted CTL specific for peptides from the leukaemia-associated antigens CD33 and CD19 were obtained with comparable efficiency. Collectively, the results show that dendritic cells engineered to express defined allo-HLA peptide complexes are highly efficient in generating CTL specifically reacting with tumour-associated antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology*
  • HLA-A2 Antigen
  • Humans
  • Immunotherapy / methods
  • Isoantigens / immunology*
  • Lymphocyte Activation / immunology
  • Peptides / immunology
  • Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection


  • Antigens, Neoplasm
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Isoantigens
  • Peptides