The effects of liposome formulations of interleukin 2 (IL-2) and local route were studied in C57BL/6 mice with MCA-106 sarcoma pulmonary metastases. IL-2 liposomes made by hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 had 95% of the IL-2 associated with the lipid fraction. When mice with pulmonary micro-metastases were treated once daily with free cytokine on days 5, 6, and 7 after tumor inoculation, the intrathoracic route was superior to the i.p. or s.c. routes. When IL-2 liposomes were administered by the local intrathoracic route, significantly better antitumor effects (P < 0.01) were seen compared to empty liposomes or free IL-2 as determined by (a) increased survival and (b) reduced numbers of pulmonary metastases. Minimal toxicity was observed. Results indicate that local route and incorporation of IL-2 in liposomes may enhance therapeutic efficacy and facilitate more practical daily dosing regimens.

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P. M. A. is a recipient of a Career Development Award from the American Cancer Society. This work was supported by the Children's Cancer Research Fund, Minnesota Medical Foundation, USPHS Training Grant T32CA09445, ACS Grant IN-13-28-1, National Cancer Institute CA Grant 49097-01, and a contract with the University of Minnesota from Oncotherapeutics, Inc.

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