Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL-2

The purpose of this study was to compare the local and systemic therapeutic effects of Interleukin-2 (IL-2) used in 3 different preparations: suspended in PBS, suspended in 2% agar, and entrapped in multi-lamellar liposomes suspended in 2% agar. The liposomes were composed of phosphatidylglycerol and phosphatidylcholine in a 1:4 molar ratio. The net release of IL-2 in vitro (by ELISA assay) at 37 degrees C, measured at 4 hr, 2 days, and 10 days, was 50%, 75%, and 100% from agar, and 8%, 22%, and 33% from liposomes in agar. In the therapeutic tests, the IL-2 preparations were injected close to s.c. implants of the MC2 mouse mammary carcinoma. Four injections at weekly intervals of IL-2 in agar had as much local and systemic (against uninjected contralateral tumor implants in treated mice) therapeutic effect as the same total amount of IL-2 in PBS given in 20 daily injections over 4 weeks. The IL-2 liposome-gel preparation was most effective (p less than 0.05), probably due to the more sustained release of IL-2. Three injections of this preparation gave a fixed and sustained peritumor release of IL-2 which, at sub-toxic levels, resulted in both local and systemic therapeutic effects.