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.
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.
1 Biogen, Inc. , Cambridge, Massachusetts.
Antonio
A
Boccia
1 Biogen, Inc. , Cambridge, Massachusetts.
Cyrus
C
Virata
2 Cleveland Clinic Foundation , Cleveland, Ohio.
Daniel
D
Lindner
1 Biogen, Inc. , Cambridge, Massachusetts.
Nicki
N
English
1 Biogen, Inc. , Cambridge, Massachusetts.
Nuzhat
N
Pathan
1 Biogen, Inc. , Cambridge, Massachusetts.
Margot
M
Brickelmaier
1 Biogen, Inc. , Cambridge, Massachusetts.
Xiao
X
Hu
1 Biogen, Inc. , Cambridge, Massachusetts.
Jennifer L
JL
Gardner
1 Biogen, Inc. , Cambridge, Massachusetts.
Liaomin
L
Peng
1 Biogen, Inc. , Cambridge, Massachusetts.
Xinzhong
X
Wang
1 Biogen, Inc. , Cambridge, Massachusetts.
Xiamei
X
Zhang
1 Biogen, Inc. , Cambridge, Massachusetts.
Lu
L
Yang
1 Biogen, Inc. , Cambridge, Massachusetts.
Keli
K
Perron
1 Biogen, Inc. , Cambridge, Massachusetts.
Grace
G
Yco
1 Biogen, Inc. , Cambridge, Massachusetts.
Rebecca
R
Kelly
1 Biogen, Inc. , Cambridge, Massachusetts.
James
J
Gamez
3 Scripps and Associates, Inc. , Evergreen, Colorado.
Thomas
T
Scripps
1 Biogen, Inc. , Cambridge, Massachusetts.
Donald
D
Bennett
1 Biogen, Inc. , Cambridge, Massachusetts.
Ingrid B
IB
Joseph
1 Biogen, Inc. , Cambridge, Massachusetts.
Darren P
DP
Baker
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011092:Polyethylene Glycols; D016899:Interferon-beta; C428112:peginterferon beta-1a
cancer; interferon beta; pegylation; xenograft