Our research activities focus upon modulation of the immune system in the treatment of patients with cancer, most notably leukemias and lymphomas, but also more recently, melanoma and other solid tumors. We have concentrated our efforts by clinical strategies to reduce the incidence and severity of graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. We have conducted several clinical trials utilizing T12, a monoclonal antibody reactive with CD6+ T cells. We have demonstrated that CD6+ T cell depletion of donor marrow, as the sole form of immune suppression, can decrease GVHD and transplant related mortality in patients receiving grafts from both related and unrelated donors. A formal comparison of this approach toward GVHD prevention to traditional approaches will be initiated in Fall 1999. We have also developed clinical strategies to address the issue of relapse after transplantation. These have included the introduction of both cytokines (IL-2) and cellular elements (CD4+ donor cells) to both prevent and treat relapse. These studies have been the basis of laboratory investigations which have been able to identify T cells with specific repertoires emerging during the generation of both alloantigen and anti-leukemic clinical activity. Further collaboration with Dr. Ritz will hopefully lead to the identification of specific antigens which can be targeted in future clinical trials. In addition to work performed on allo-immunity, we have participated in clinical trials to induce autologous anti-tumor immunity. Working in collaboration with Dr Glenn Dranoff at DFCI, we documented the generation of tumor immunity through vaccination of melanoma patients with irradiated autologous tumor cells genetically engineered to secrete GM-CSF. As with our efforts in allo-reactivity, further clinical and laboratory work will lead to the identification of specific target and effector cells that can be utilized in future therapeutic trials.