T cell receptor gene therapy for autoimmune diseases

Ann N Y Acad Sci. 2007 Sep:1110:222-32. doi: 10.1196/annals.1423.024.

Abstract

The current quality of autoimmune disease treatments is not satisfactory in regard to efficacy and safety. Antigen-specific immunotherapy is a future therapy that could achieve maximal efficacy with minimal adverse effects. T cells are essential components in antigen-specific immunity. However, we do not have a sufficient strategy for manipulating antigen-specific T cells. We propose that T cell receptor (TCR) gene transfer is a hopeful approach for antigen-specific immunotherapy. We confirmed the efficacy of TCR gene therapy in animal models of systemic autoimmune disease and arthritis. In lupus-prone NZB/W F1 mice, nucleosome-specific TCR and CTLA4Ig transduced cells suppressed autoantibody production and nephritis development. In the therapeutic experiment of collagen-induced arthritis (CIA), arthritis-related TCRs were isolated from single T cells accumulating in the arthritis site. Arthritis-related TCR and TNFRIg transduced cells or TCR and Foxp3 transduced cells suppressed arthritis progression and bone destruction. Therefore, engineered antigen-specific cells manipulated to express appropriate functional genes could be applied to specific immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • Forkhead Transcription Factors / metabolism
  • Genetic Therapy*
  • Humans
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Forkhead Transcription Factors
  • Receptors, Antigen, T-Cell