University of Michigan researchers have been in the forefront in the investigation of treating tumors by the direct intratumoral inoculation of a foreign gene encoding a transplantation antigen known as, HLA-B7. In initial clinical studies, the intratumoral inoculation of this complex with liposomes induces an inflammatory response within the tumor, expression of the foreign transplantation antigen on tumor cells, infiltration of T lymphocytes within the tumor; and, regression of the injected nodules in a small subgroup of patients. These preliminary studies also demonstrated that the TIL extracted from the tumor prior to treatment and compared to post treatment demonstrated enhanced ability of the TIL cells to recognize and respond to tumor antigen. In this protocol, we propose to administer HLA-B7 gene complex with liposomes into melanoma tumors which will subsequently be excised for the generation of tumor infiltrating lymphocytes (TIL). In pre-clinical and clinical studies of TIL, the infusion of TIL cells has resulted in the regression of established, advanced tumor burdens. This form of therapy is known as adoptive therapy. It is hypothesized that the expression of the foreign MHC gene results in an inflammatory milieu within the tumor which allows enhanced sensitization of infiltrating T cells to respond to tumor antigens. Based on these preliminary studies, we have initiated this clinical protocol to determine the feasibility of generating TIL derived from HLA-B7 transfected tumors for subsequent adoptive immunotherapy. Additional studies will be performed on the TIL to evaluate their immunological function both pre and post gene transfer.
Showing the most recent 10 out of 1380 publications
