Interleukin-12: biological properties and clinical application.
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-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.
Del Vecchio
Michele
M
Medical Oncology Unit 2, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Italy.
Bajetta
Emilio
E
Canova
Stefania
S
Lotze
Michael T
MT
Wesa
Amy
A
Parmiani
Giorgio
G
Anichini
Andrea
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy; D014611:Vaccination
D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018664:Interleukin-12