Interleukin-18: Biology and Role in the Immunotherapy of Cancer
Abstract:Interleukin-18 (IL-18) is an immunostimulatory cytokine belonging to the IL-1 family. IL-18 can regulate both innate and adaptive immune responses through its effects on natural killer (NK) cells, monocytes, dendritic cells, T cells, and B cells. IL-18 acts synergistically with other pro-inflammatory cytokines to promote interferon-γ (IFN-γ) production by NK cells, T cells, and possibly other cell types. Systemic administration of IL-18 has been shown to have significant antitumor activity in several preclinical animal models. Phase I clinical trials of recombinant human IL-18 have demonstrated that it can be safely administered to patients with advanced cancer. Biologic effects of IL-18 therapy include activation of monocytes, NK cells, and T cells and production of IFN-γ as well as other cytokines in vivo. A phase II study of IL-18 in patients with metastatic melanoma confirmed its safety but suggested limited efficacy of IL-18 monotherapy in this setting. IL-18 appears to act predominantly as a costimulatory cytokine and its optimal use for cancer immunotherapy may be in combination with other immunostimulatory cytokines, vaccines, or monoclonal antibodies.
Keywords: CD4+ T cells; CLINICAL TRIALS; Chemotherapy; Cytokine; Gene Therapy; ICAM-1; IL-1 family; IRAK; Interleukin-18; MCA205; Melanoma; MyD88; Rituximab; STAT; Stem Cell Transplantation; T cell; TRAF6; VCAM-1; adenovirus; antibodies; carcinogenesis; chemotherapeutic agents; endothelial cells; fibroblasts; immunotherapy; interferon-γ; interleukin-12; monoclonal antibodies; monocytes; natural killer cell; prostate specific antigen; rituximab; vaccines
Document Type: Research Article
Publication date: October 1, 2010
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