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Interleukin-18: Biology and Role in the Immunotherapy of Cancer

[ Vol. 17 , Issue. 29 ]

Author(s):

S. Srivastava, N. Salim and M. J. Robertson   Pages 3353 - 3357 ( 5 )

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:

Cytokine,immunotherapy,natural killer cell,T cell,rituximab,interferon-γ,Interleukin-18,IL-1 family,interleukin-12,carcinogenesis,MyD88,IRAK,TRAF6,ICAM-1,VCAM-1,endothelial cells,fibroblasts,antibodies,CD4+ T cells,MCA205,Gene Therapy,prostate specific antigen,adenovirus,Chemotherapy,Stem Cell Transplantation,STAT,CLINICAL TRIALS,Melanoma,monocytes,monoclonal antibodies,vaccines,chemotherapeutic agents

Affiliation:

, , Bone Marrow and Stem Cell Transplantation Program, Indiana University Medical Center, Walther Hall R3-C412, 980 West Walnut Street, Indianapolis, IN 46202, USA.



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