IMMUNE-RESPONSE IN HUMAN-MELANOMA AFTER TRANSFER OF AN ALLOGENEIC CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX GENE WITH DNA-LIPOSOME COMPLEXES

Analysis of the antitumor immune response after gene transfer of a for eign major histocompatibility complex class I protein, HLA-B7, was per formed. Ten HLA-B7-negative patients with stage IV melanoma were treat ed in an effort to stimulate local tumor immunity. Plasmid DNA was det ected within treated tumor nodules, and RNA encoding recombinant HLA-B 7 or HLA-B7 protein was demonstrated in 9 of 10 patients. T cell migra tion into treated lesions was observed and tumorinfiltrating lymphocyt e reactivity was enhanced in six of seven and two of two patients anal yzed, respectively. In contrast, the frequency of cytotoxic T lymphocy te against autologous tumor in circulating peripheral blood lymphocyte s was not altered significantly, suggesting that peripheral blood lymp hocyte reactivity is not indicative of local tumor responsiveness. Loc al inhibition of tumor growth was detected after gene transfer in two patients, one of whom showed a partial remission. This patient subsequ ently received treatment with tumor-infiltrating lymphocytes derived f rom gene-modified tumor, with a complete regression of residual diseas e. Thus, gene transfer with DNA-liposome complexes encoding an allogen eic major histocompatibility complex protein stimulated local antitumo r immune responses that facilitated the generation of effector cells f or immunotherapy of cancer.