Interleukin-12: biological properties and clinical application

M Del Vecchio, E Bajetta, S Canova, MT Lotze… - Clinical Cancer …, 2007 - AACR
M Del Vecchio, E Bajetta, S Canova, MT Lotze, A Wesa, G Parmiani, A Anichini
Clinical Cancer Research, 2007AACR
Abstract 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-γ 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-γ …
Abstract
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-γ 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-γ–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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