Antigen-specific T cell-mediated gene therapy

Autoantigen-specific T cells have tissue-specific homing properties which make them ideal vehicles for the local delivery of immunoregulatory molecules. In May 15 Journal of Clinical Investigation Atsuo Nakajima and colleagues from Stanford University show that antigen-specific T cell-mediated gene therapy can inhibit the development of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis.

Nakajima et al used type II collagen-specific (CII-specific) CD4+ T hybridomas or primary CD4+ T cells after gene transfer, as vehicles to deliver the IL-12 antagonist, IL-12 p40 — an immunoregulatory protein for the treatment of CIA. Transfer of engineered CII-reactive T-cell hybridomas significantly inhibited the development of CIA, while cells transduced with vector control had no effect. In vivo cell detection showed that transferred CII-reactive T-cell hybridomas accumulated in inflamed joints in mice with CIA (J Clin Invest 2001, 107:1293-1301).

These results suggest that the delivery of therapeutic proteins via antigen-specific T cells could be ...