Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies

Haematologica. 2011 Mar;96(3):477-81. doi: 10.3324/haematol.2010.025916. Epub 2010 Nov 25.

Abstract

To broaden the applicability of adoptive T-cell therapy for the treatment of hematologic malignancies, we aim to start a clinical trial using HA-1-TCR transferred virus-specific T cells. TCRs directed against the minor histocompatibility antigen (MiHA) HA-1 are good candidates for TCR gene transfer to treat hematologic malignancies because of the hematopoiesis-restricted expression and favorable frequency of HA-1. For optimal anti-leukemic reactivity, high cell-surface expression of the introduced TCR is important. Previously, however, we have demonstrated that gene transferred HA-1-TCRs are poorly expressed at the cell-surface. In this study several strategies were explored to improve expression of transferred HA-1-TCRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genes, T-Cell Receptor / genetics*
  • Genes, T-Cell Receptor / immunology
  • Genetic Therapy / methods
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy, Adoptive / methods
  • Minor Histocompatibility Antigens / genetics*
  • Minor Histocompatibility Antigens / immunology
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Retroviridae / genetics
  • Retroviridae / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Transduction, Genetic

Substances

  • Minor Histocompatibility Antigens
  • Receptors, Antigen, T-Cell