Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma

We vaccinated metastatic melanoma patients with irradiated, autologous mela noma cells genetically engineered to secrete interleukin 2 (IL-2) to invest igate whether an anti-tumor immune response would be induced, Melanoma cell cultures were established from surgical specimens and were engineered to s ecrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tol erated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed a nti-tumor DTH after the first vaccination and showed an increased response after the second vaccination, Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical res ponses were seen, but three patients had stable disease for 7-15 months, on e of whom has not yet progressed (15+ months), Thus, patient vaccination,vi th autologous, genetically engineered tumor cells is feasible and safe, Ant i-tumor DTH and CTLs can be induced in some patients with such a vaccine.