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Interleukin-12: Biological Properties and Clinical Application

Authors' Affiliations: ¹ Medical Oncology Unit 2 and ² Human Tumor Immunobiology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, ³ Unit of Immuno-Biotherapy of Solid Tumors, Istituto Scientifico S. Raffaele, Milan, Italy, ⁴ Translational Research, Molecular Medicine Institute, University of Pittsburgh Cancer Institute, and ⁵ Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Emilio Bajetta, Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. Phone: 39-02-23902500; Fax: 39-02-23902149; E-mail: emilio.bajetta{at}istitutotumori.mi.it.

Interleukin-12 (IL-12) is a heterodimeric protein, first recovered from EBV-transformed B cell lines. It is a multifunctional cytokine, the properties of which bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation. By promoting IFN- production, proliferation, and cytolytic activity of natural killer and T cells, IL-12 induces cellular immunity. In addition, IL-12 induces an antiangiogenic program mediated by IFN-–inducible genes and by lymphocyte-endothelial cell cross-talk. The immunomodulating and antiangiogenic functions of IL-12 have provided the rationale for exploiting this cytokine as an anticancer agent. In contrast with the significant antitumor and antimetastatic activity of IL-12, documented in several preclinical studies, clinical trials with IL-12, used as a single agent, or as a vaccine adjuvant, have shown limited efficacy in most instances. More effective application of this cytokine, and of newly identified IL-12 family members (IL-23 and IL-27), should be evaluated as therapeutic agents with considerable potential in cancer patients.

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