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T Cell Receptor Gene Therapy for Autoimmune Diseases
Author(s) -
FUJIO KEISHI,
OKAMURA TOMOHISA,
OKAMOTO AKIKO,
YAMAMOTO KAZUHIKO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1423.024
Subject(s) - t cell receptor , immunology , arthritis , immunotherapy , medicine , antigen , autoimmune disease , genetic enhancement , t cell , cancer research , biology , immune system , antibody , gene , biochemistry
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 .