Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity

Blood. 2009 Sep 3;114(10):2131-9. doi: 10.1182/blood-2009-03-209387. Epub 2009 Jul 8.


Adoptive transfer of T cells expressing transgenic T-cell receptors (TCRs) with antitumor function is a hopeful new therapy for patients with advanced tumors; however, there is a critical bottleneck in identifying high-affinity TCR specificities needed to treat different malignancies. We have developed a strategy using autologous dendritic cells cotransfected with RNA encoding an allogeneic major histocompatibility complex molecule and a tumor-associated antigen to obtain allo-restricted peptide-specific T cells having superior capacity to recognize tumor cells and higher functional avidity. This approach provides maximum flexibility because any major histocompatibility complex molecule and any tumor-associated antigen can be combined in the dendritic cells used for priming of autologous T cells. TCRs of allo-restricted T cells, when expressed as transgenes in activated peripheral blood lymphocytes, transferred superior function compared with self-restricted TCR. This approach allows high-avidity T cells and TCR specific for tumor-associated self-peptides to be easily obtained for direct adoptive T-cell therapy or for isolation of therapeutic transgenic TCR sequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Humans
  • Isoantigens / genetics
  • Isoantigens / immunology*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Peptides / genetics
  • Peptides / immunology*
  • RNA / genetics
  • RNA / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology*
  • Transfection


  • Antigens, Neoplasm
  • HLA Antigens
  • Isoantigens
  • Peptides
  • Receptors, Antigen, T-Cell
  • RNA