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Updated: Jul 11, 2026

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
Published on: September 10, 2017
T cell receptor gene therapy for autoimmune diseases
Keishi Fujio1, Tomohisa Okamura, Akiko Okamoto
1Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113, Japan. kfujio-tky@umin.ac.jp
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.
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