Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2 transfected cancer cells: Outcome of a phase I study

We performed a phase I trial to evaluate the safety and tolerability of rep eated skin injections of IL-2-transfected autologous melanoma cells into pa tients,vith advanced disease. Cell suspensions, propagated from excised met astases, were IL-2 gene transfected by adenovirus-enhanced transferrinfecti on and X-irradiated prior to injection, Vaccine production was successful i n 54% of the patients. Fifteen patients (37%) received two to eight skin va ccinations of either 3 X 10(6) (intradermal) or 1 X 10(7) (half intradermal , half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/2 4 hr), Analyses of safety and efficacy were carried out in 15 and 14 patien ts, respectively. Overall, the vaccine was well tolerated. All patients dis played modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and in creasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibo dy titers (1 of 15), recipients developed de novo or exhibited increased me lanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15 ) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15), Th is supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, b ut five of them experienced periods of disease stabilization. Three of thes e individuals received more than the four planned vaccinations and their me an survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, aut ologous cancer cells can be safely administered to stage IV melanoma patien ts and could conceivably be of benefit to patients with less advanced disea se.