Antitumor activity of interleukin 12 in preclinical models

• Published in: Cancer chemotherapy and pharmacology Vol. 38 Suppl; p. S16
• Main Authors: Brunda, M J, Luistro, L, Rumennik, L, Wright, R B, Dvorozniak, M, Aglione, A, Wigginton, J M, Wiltrout, R H, Hendrzak, J A, Palleroni, A V
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1996
• Subjects: Animals; Drug Screening Assays, Antitumor; Humans; Interleukin-12 - immunology; Interleukin-12 - therapeutic use; Interleukin-2 - therapeutic use; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Tumor Cells, Cultured - drug effects
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800051031

Interleukin 12 (IL-12) is a heterodimeric cytokine with a number of biological effects that are consistent with its potential role as an antitumor agent. The antimetastatic and antitumor activities of IL-12 have been demonstrated in a number of murine tumor models. Both the inhibition of established experimental pulmonary or hepatic metastases and a reduction in spontaneous metastases have been achieved by treatment with murine IL-12. Systemic treatment of mice bearing subcutaneous tumors with IL-12 results in tumor growth inhibition, prolongation of survival, and, in some models, tumor regression. The antitumor effect of IL-12 in these models is dose-dependent and can be initiated against well-established tumors. Mice cured of their tumor by IL-12 treatment are specifically immune to rechallenge with the same tumor. A series of experiments have demonstrated that both T-cells and interferon-gamma (IFN-gamma) induction are necessary for the optimal antitumor effects of IL-12. However, the antitumor efficacy of IL-12 has not been observed after exogenous administration of murine IFN-gamma, suggesting that additional factors may be important for the antitumor effects of IL-12. In several tumor models, IL-12 is more active or has a larger therapeutic window than either IL-2 or IFN-alpha, two cytokines with demonstrated antitumor activity against human malignancies. Combining IL-12 with other cytokines or chemotherapeutic drugs can improve antitumor effects.