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Interleukin-12: biological properties and clinical application Del Vecchio M; Bajetta E; Canova S; Lotze MT; Wesa A; Parmiani G; Anichini AClin Cancer Res 2007[Aug]; 13 (16): 4677-85Interleukin-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-gamma 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-gamma-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.|Adjuvants, Immunologic/pharmacology[MESH]|Angiogenesis Inhibitors/pharmacology/therapeutic use[MESH]|Animals[MESH]|Antibodies, Monoclonal/therapeutic use[MESH]|Antineoplastic Agents/therapeutic use[MESH]|Genetic Therapy[MESH]|Humans[MESH]|Immunity, Innate[MESH]|Interleukin-12/genetics/pharmacology/*physiology/*therapeutic use[MESH]|Neoplasms/drug therapy[MESH]|Vaccination[MESH] |
