Antitumor and Antimetastatic Activity of Interleukin 12 against Murine Tumors

Antitumor and Antimetastatic Activity of Interleukin 12 against Murine Tumors

October 1993 | Michael J. Brunda, Leopoldo Luistro, Rajeev R. Warrier, Rosemary B. Wright, Brian R. Hubbard, Molly Murphy, Stanley F. Wolf, Maurice K. Gately
This study evaluates the antitumor and antimetastatic effects of murine interleukin-12 (IL-12) in various murine tumor models. IL-12 treatment significantly reduced the growth of B16F10 melanoma tumors and experimental pulmonary and hepatic metastases, as well as subcutaneous M5076 reticulum cell sarcoma and Renca renal cell adenocarcinoma tumors. Systemic administration of IL-12 increased survival time and inhibited tumor growth, while local peritumoral injections led to tumor regression. IL-12 was effective in NK cell-deficient beige mice and in mice depleted of NK cell activity, suggesting that NK cells are not the primary mediators of its antitumor effects. However, its efficacy was greatly reduced in nude mice, indicating the involvement of T cells. Depletion of CD8+ T cells significantly reduced IL-12 efficacy, highlighting their critical role in mediating antitumor effects against subcutaneous tumors. IL-12 is a heterodimeric cytokine composed of p40 and p35 subunits. It enhances NK and T cell activity, increases cytotoxic activity, and induces IFN-γ secretion. These properties suggest that IL-12 could be used as an immunomodulatory cytokine in cancer therapy. The study demonstrates that IL-12 has potent antitumor and antimetastatic effects in murine models, with its efficacy primarily mediated through CD8+ T cells. The results indicate that IL-12 has significant potential as a therapeutic agent for malignancies.This study evaluates the antitumor and antimetastatic effects of murine interleukin-12 (IL-12) in various murine tumor models. IL-12 treatment significantly reduced the growth of B16F10 melanoma tumors and experimental pulmonary and hepatic metastases, as well as subcutaneous M5076 reticulum cell sarcoma and Renca renal cell adenocarcinoma tumors. Systemic administration of IL-12 increased survival time and inhibited tumor growth, while local peritumoral injections led to tumor regression. IL-12 was effective in NK cell-deficient beige mice and in mice depleted of NK cell activity, suggesting that NK cells are not the primary mediators of its antitumor effects. However, its efficacy was greatly reduced in nude mice, indicating the involvement of T cells. Depletion of CD8+ T cells significantly reduced IL-12 efficacy, highlighting their critical role in mediating antitumor effects against subcutaneous tumors. IL-12 is a heterodimeric cytokine composed of p40 and p35 subunits. It enhances NK and T cell activity, increases cytotoxic activity, and induces IFN-γ secretion. These properties suggest that IL-12 could be used as an immunomodulatory cytokine in cancer therapy. The study demonstrates that IL-12 has potent antitumor and antimetastatic effects in murine models, with its efficacy primarily mediated through CD8+ T cells. The results indicate that IL-12 has significant potential as a therapeutic agent for malignancies.
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