VACCINATION WITH IRRADIATED AUTOLOGOUS MELANOMA-CELLS ENGINEERED TO SECRETE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENERATES POTENT ANTITUMOR IMMUNITY IN PATIENTS WITH METASTATIC MELANOMA

We conducted a Phase I clinical trial investigating the biologic activ ity of vaccination with irradiated autologous melanoma cells engineere d to secrete human granulocytemacrophage colony-stimulating factor in patients with metastatic melanoma, Immunization sites were intensely i nfiltrated with T lymphocytes, dendritic cells, macrophages, and eosin ophils in all 21 evaluable patients. Although metastatic lesions resec ted before vaccination were minimally infiltrated with cells of the im mune system in all patients, metastatic lesions resected after vaccina tion were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and anti body responses were associated with tumor destruction. These results d emonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melano ma.