Michael Blaese's laboratory continues to focus on the development of gene therapy. He led the group which performed the first authorized use of gene transfer to treat human disease when they infused 10/9 autologous ADA gene-corrected T cells into a 4-yr-old girl with ADA deficiency SCID. Retroviral vectors were used to insert a normal human ADA gene into this girl's polyclonal peripheral blood T cells which had been stimulated in tissue culture with an anti-T cell receptor monoclonal antibody and IL-2. The gene-corrected T cells were expanded 100-1000 fold and then returned intravenously within 2 weeks to maintain a polyclonal repertoire. This girl and a second ADA deficient patient have been treated 10-12 times over the past two years with such gene-corrected T cell infusions and are now each showing signs of reconstituted immune reactivity including the production of isohemagglutinins and DTH in response to environmental antigenic stimulation. Dr. Blaese's laboratory has also developed a unique new approach to direct gene therapy of cancer using inoculation of murine fibroblasts producing retroviral vectors directly into tumors in situ. Using vectors containing the gene for herpes simplex thymidine kinase, he has shown cure of brain tumors in rats following systemic administration of the anti-herpes virus drug Ganciclovir. In addition to our ongoing clinical and laboratory evaluation of other immunodeficiency disorders such as the Wiskott-Aldrich syndrome, work has also continued on the development of succinylacetone (SA) as a clinically useful immunosuppressive compound. We have shown that SA has profound dual system immunosuppressive effects in rats, mice, dogs, miniature swine and non-human primates. It is effective in preventing allograft rejection, graft vs host disease (GVHD), antibody production in these experimental animal models and has shown utility in treating several different autoimmune disorders including experimental autoimmune uveitis and adjuvant arthritis.
