Antitumor and Antimetastatic Activity of Interleukin 12 against Murine Tumors

Antitumor and Antimetastatic Activity of Interleukin 12 against Murine Tumors

Volume 178 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 investigates the antitumor and antimetastatic effects of murine interleukin 12 (IL-12) against various murine tumors. IL-12 administration to mice resulted in enhanced cytotoxic natural killer (NK) cell and cytolytic T cell activity, as well as increased interferon γ (IFN-γ) secretion. The study found that IL-12 significantly reduced experimental pulmonary metastases and subcutaneous growth of the B16F10 melanoma, with a dose-dependent increase in survival time. IL-12 was also effective against established hepatic metastases and subcutaneous M5076 reticulum cell sarcoma and Renca renal cell adenocarcinoma tumors, without causing gross toxicity. Local peritumoral injections of IL-12 into established subcutaneous Renca tumors led to regression and complete disappearance of these tumors. The antitumor efficacy of IL-12 was mediated primarily through CD8+ T cells, as demonstrated by the reduced efficacy in nude mice and the depletion of CD8+ T cells. These findings highlight the potent antitumor and antimetastatic properties of IL-12 and the critical role of CD8+ T cells in mediating its effects.This study investigates the antitumor and antimetastatic effects of murine interleukin 12 (IL-12) against various murine tumors. IL-12 administration to mice resulted in enhanced cytotoxic natural killer (NK) cell and cytolytic T cell activity, as well as increased interferon γ (IFN-γ) secretion. The study found that IL-12 significantly reduced experimental pulmonary metastases and subcutaneous growth of the B16F10 melanoma, with a dose-dependent increase in survival time. IL-12 was also effective against established hepatic metastases and subcutaneous M5076 reticulum cell sarcoma and Renca renal cell adenocarcinoma tumors, without causing gross toxicity. Local peritumoral injections of IL-12 into established subcutaneous Renca tumors led to regression and complete disappearance of these tumors. The antitumor efficacy of IL-12 was mediated primarily through CD8+ T cells, as demonstrated by the reduced efficacy in nude mice and the depletion of CD8+ T cells. These findings highlight the potent antitumor and antimetastatic properties of IL-12 and the critical role of CD8+ T cells in mediating its effects.
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