Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice.

摘要: Cellular IL-10 (cIL-10), the collective term for human and murine IL-10, has both stimulatory inhibitory effects on diverse cell types, including costimulation of T proliferation, chemoattraction CD8+ cells, stimulation lymphokine-activated killer activity. Human (hIL-10) differs from its EBV homolog viral (vIL-10) by only 16% at amino acid level; however, vIL-10 shares with cIL-10 predominantly effects, such as macrophage deactivation. We administered systemically to mice bearing established (day 7) sarcomas, melanomas, or colorectal carcinomas. At high doses (20 60 micrograms/day x 7 days), induced rejection tumors, delaying tumor outgrowth resulting in complete cure. Sublethal irradiation (500 rad) prior inoculation abrogated effect. Cured were immune subsequent rechallenge 10-fold higher same, but not a different, tumor. IL-12 also potent antitumor activity interacts complementary antagonistic ways; co-administration cytokines resulted additive To compare vs vivo, we engineered CL8-1 melanoma transfectants (mIL-10) gene. Local secretion mIL-10 while accelerated outgrowth. Subsequent systemic administration vIL-10-transduced tumors completely reversed local suppressive leading rejection, suggesting distinct pathways effects. That can stimulate acquisition an effective, specific, long-lived response models reverse immunosuppressive indicates potential role biologic therapy cancer suggests broader interpretation biology.