Antitumor effects of liposomal IL1? and TNF? against the pulmonary metastases of the B16F10 murine melanoma in syngeneic mice

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Abstract
Interleukin 1 alpha (IL1α) and tumor necrosis factor alpha (TNFα) have been successfully incorporated into specific phosphatidylcholine (PC) and phosphatidylserine (PS) multilamellar vesicle (MLV) liposomes by modifying the concentration of calcium ion and pH of the encapsulation buffer. Under these conditions, some of the cytokines may attach to the exterior surface of the MLV and therefore be readily accessible to target cells for receptor binding and signal transduction. These cytokine-associated liposomes are stable for up to 2 weeks in serum-free buffer, and leakage of cytokines into medium containing 10% fetal bovine serum was about 50% at the end of a 3-day incubation period at 37°C. The biological activities mediated by liposomal IL1α and TNFα were specific: the stimulation of thymidine uptake in T-helper D10 lymphocytes and the cytolysis of TNFα-sensitive L929 target cells could be blocked by specific neutralizing antibodies in a dose-dependent fashion. When administered intravenously into C57BL/6 mice bearing the syngeneic B16F10 murine melanoma cells, dual entrapment of liposomal IL1α and TNFα significantly reduced the number of metastatic tumor nodules in the lungs and prolonged the life span of the animals. Thus, liposomal IL1α and TNFα displayed significant in vivo antitumor activity against the IL1α- and TNFα-resistant B16F10 metastatic murine melanoma.

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