Cytokine depot formulations as adjuvants for tumor vaccines. I. Liposome-encapsulated IL-2 as a depot formulation

In an attempt to mimic cytokine gene-transfected tumor cells and to develop an alternative approach to cancer immunotherapy, the authors vaccinated mi ce with mixtures of inactivated tumor cells and cytokine-containing depots. The RenCa mouse renal carcinoma and the B16 mouse melanoma were used as an imal tumor models, with interleukin-2 (IL-2) as a cytokine and liposomes as a depot form. The results obtained show that vaccines consisting of mixtur es of irradiated tumor cells and cytokine-containing liposomes can be used as highly effective tumor vaccines. These vaccines are very easy to prepare and, in contrast to vaccines consisting of cytokine gene transfected tumor cells, their composition (cell dosage, cytokine dosage) can be easily vari ed. Vaccination efficiency depended on (a) on the immunogenicity of the tum or cells: RenCa tumor cells are more immunogenic than B16 melanoma cells; ( b) vaccination frequency: a single vaccination with irradiated tumor cells and 10 mu g of IL-2 in liposome-encapsulated form was sufficient to induce lasting protective immunity against the RenCa tumor, whereas several (four to six) vaccinations in weekly intervals were needed to obtain a similar de gree of protective immunity to the B16 melanoma; and (c) the dose of the cy tokine encapsulated in the admired liposome depots: immunity to the tumors could be induced only within a narrow cytokine-dose range ("IL-2-dose windo w"). The results obtained indicate that, because of the easiness of prepara tion and handling, vaccine formulations consisting of irradiated tumor cell s and IL-2 in depot formulations are candidates for tumor vaccines for the treatment of tumor patients.