2. Academic Validation
  3. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models

Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models

  • J Interferon Cytokine Res. 2017 Jan;37(1):20-31. doi: 10.1089/jir.2016.0027.
Antonio Boccia 1,  Cyrus Virata 1,  Daniel Lindner 2,  Nicki English 1,  Nuzhat Pathan 1,  Margot Brickelmaier 1,  Xiao Hu 1,  Jennifer L Gardner 1,  Liaomin Peng 1,  Xinzhong Wang 1,  Xiamei Zhang 1,  Lu Yang 1,  Keli Perron 1,  Grace Yco 1,  Rebecca Kelly 1,  James Gamez 1,  Thomas Scripps 3,  Donald Bennett 1,  Ingrid B Joseph 1,  Darren P Baker 1
Affiliations

Affiliations

  • 1 1 Biogen, Inc. , Cambridge, Massachusetts.
  • 2 2 Cleveland Clinic Foundation , Cleveland, Ohio.
  • 3 3 Scripps and Associates, Inc. , Evergreen, Colorado.
PMID: 27835061 DOI: 10.1089/jir.2016.0027
Abstract

Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved Anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK Inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved Anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

Keywords

cancer; interferon beta; pegylation; xenograft.

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