Antitumor activity of interleukin 12 in preclinical models.
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.
Brunda
M J
MJ
Department of Oncology, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Luistro
L
L
Rumennik
L
L
Wright
R B
RB
Dvorozniak
M
M
Aglione
A
A
Wigginton
J M
JM
Wiltrout
R H
RH
Hendrzak
J A
JA
Palleroni
A V
AV
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007376:Interleukin-2; D018664:Interleukin-12