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- April 19, 2013 at 1:50 am
Immunomodulatory Effects of Interferons in Malignancies
To cite this article:
Joseph Bekisz, Yuki Sato, Chase Johnson, Syed R. Husain, Raj K. Puri, and Kathryn C. Zoon. Journal of Interferon & Cytokine Research. April 2013, 33(4): 154-161. doi:10.1089/jir.2012.0167.Published in Volume: 33 Issue 4: April 9, 2013
Immunomodulatory Effects of Interferons in Malignancies
To cite this article:
Joseph Bekisz, Yuki Sato, Chase Johnson, Syed R. Husain, Raj K. Puri, and Kathryn C. Zoon. Journal of Interferon & Cytokine Research. April 2013, 33(4): 154-161. doi:10.1089/jir.2012.0167.Published in Volume: 33 Issue 4: April 9, 2013
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Joseph Bekisz,1 Yuki Sato,2 Chase Johnson,1 Syed R. Husain,2 Raj K. Puri,2 and Kathryn C. Zoon11Cytokine Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.2Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.Address correspondence to:Dr. Kathryn ZoonDivision of Intramural ResearchNational Institute of Allergy and Infectious DiseasesNational Institutes of Health
Bldg 33, Rm 2N09G.233 North DriveBethesda, MD 20892E-mail: kzoon@niaid.nih.gov
Received 19 December 2012
Accepted 28 January 2013ABSTRACT
Investigation of the antitumor and immunomodulatory activities of interferon (IFN) began shortly after the cytokine was discovered in 1957. Early work showed a direct correlation between administration of IFN and inhibition of symptoms associated with virally induced leukemia in mice as well as an increase in their survival time. Subsequent studies with purified IFNs confirmed the direct and indirect stimulation of immune cells, resulting in antitumor activities of IFN. Clinically, IFN-alphas (αs) have been shown to have activity against a variety of tumors. Initially, the U.S. Food and Drug Administration licensed 2 recombinant IFN-αs for the treatment of hairy-cell leukemia and then later for several other cancers. The success rate seen with IFNs and certain tumors has been varied. Unfortunately, some neoplasms show no response to IFN. Monocytes/macrophages play an important role in cancer progression. Monocytes in combination with IFN may be an important therapy for several cancers. This article focuses on the role of IFN and monocytes alone or in combination in affecting malignancies.
Introduction
Interferon (IFN) was defined as an antiviral agent by Isaacs and Lindenmann (1957) and by Paucker and others (1962) for its antigrowth activity. Intron-A (IFN-α2b, recombinant; Schering-Plough) and Roferon-A (IFN-α2a, recombinant; Hoffmann-La Roche, Nutley, N.J.) were the first IFNs licensed by the U.S. Food and Drug Administration (USFDA) for the treatment of hairy-cell leukemia. This event was indeed a milestone and served to introduce biotechnology-derived products for the treatment of cancer. Later, the USFDA licensed Intron-A and Roferon-A for AIDS-related Kaposi's sarcoma (1988). Subsequently, Intron-A was licensed by the USFDA for malignant melanoma (1995) and follicular lymphoma (1997), and Roferon-A was licensed for chronic myelogenous leukemia (1995). IFN-γ1b (Actimmune) was licensed by the USFDA in 1991 for the treatment of chronic granulomatous disease and in 2000 for the treatment of malignant osteopetrosis. The primary functions associated with IFN-γ are related to host defense and immunomodulation (e.g., antiviral defense and MHC class I upregulation), but its antitumor effects have been widely examined. Studies show that IFN-γ plays an important role in tumor surveillance. In addition to antitumor effects associated with the immune system, IFN-γ affects tumors directly by virtue of its antiangiogenic and antiproliferative properties (Miller and others 2009). IFN-γ has been used for the treatment of various malignancies, including ovarian and colorectal cancers, as well as in combination with IFN-α in the treatment of chronic myelogenous leukemia, although with mixed results (Zaidi and Merlino 2011). Interestingly, IFN-γ has not been approved as a single agent by the USFDA for any malignancy.
Although Type I and II IFNs were used with varying success with certain neoplasms, exploration and possible enhancement of the components that contribute to these effects are, therefore, of great interest. This review will focus on some of the mechanisms of IFN signaling related to the antitumor and immunomodulatory activities associated with Type I and II IFNs that lead to cell death in vitro and in vivo. The role of immune cells, especially monocytes, and their interaction with IFN and their resultant antitumor activity will be discussed.
Article full text continues at link above. Pretty technical stuff.
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