In vivo tumor suppression by adenovirus-mediated interferon α2b gene delivery

被引:25
作者
Ahmed, CMI [1 ]
Sugarman, BJ [1 ]
Johnson, DE [1 ]
Bookstein, RE [1 ]
Saha, DP [1 ]
Nagabhushan, TL [1 ]
Wills, KN [1 ]
机构
[1] Canji Inc, San Diego, CA 92121 USA
关键词
D O I
10.1089/10430349950019200
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A replication-deficient adenovirus encoding human interferon alpha 2b, driven by the human cytomegalovirus (CMV) promoter, was constructed and characterized. This construct was used to infect human cells derived from different types of cancer, The production of protein and its secretion into the culture medium were tested by Western blotting and immunoassay, Inhibition of cell proliferation and antiviral activity, two of the most important biological activities of interferon, were observed with this construct. PC-3 cells, derived from human prostatic cancer, or Hep3B cells, derived from human hepatocellular carcinoma, were injected subcutaneously to generate and establish in vivo tumors in athymic nude mice. Intratumoral injection with the recombinant adenovirus expressing interferon alpha 2b resulted in complete regression of tumor growth. Our results demonstrate that interferon gene delivery using recombinant adenoviral vectors may be a useful approach to treat a variety of cancers.
引用
收藏
页码:77 / 84
页数:8
相关论文
共 22 条
[1]   NATURAL HUMAN INTERFERON-ALPHA-2 IS O-GLYCOSYLATED [J].
ADOLF, GR ;
KALSNER, I ;
AHORN, H ;
MAURERFOGY, I ;
CANTELL, K .
BIOCHEMICAL JOURNAL, 1991, 276 :511-518
[2]   ADENOVIRUS EARLY REGION-1A MODULATION OF INTERFERON ANTIVIRAL ACTIVITY [J].
ANDERSON, KP ;
FENNIE, EH .
JOURNAL OF VIROLOGY, 1987, 61 (03) :787-795
[3]  
Bordens Ronald, 1997, Seminars in Oncology, V24, P41
[4]  
Graham F L, 1991, Methods Mol Biol, V7, P109, DOI 10.1385/0-89603-178-0:109
[5]   CHARACTERISTICS OF A HUMAN CELL LINE TRANSFORMED BY DNA FROM HUMAN ADENOVIRUS TYPE-5 [J].
GRAHAM, FL ;
SMILEY, J ;
RUSSELL, WC ;
NAIRN, R .
JOURNAL OF GENERAL VIROLOGY, 1977, 36 (JUL) :59-72
[6]   REPRESSION OF THE INTERFERON SIGNAL TRANSDUCTION PATHWAY BY THE ADENOVIRUS E1A ONCOGENE [J].
GUTCH, MJ ;
REICH, NC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (18) :7913-7917
[7]   CYTOKINE THERAPEUTICS - LESSONS FROM INTERFERON-ALPHA [J].
GUTTERMAN, JU .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (04) :1198-1205
[8]   PURIFICATION OF A TYPE-5 RECOMBINANT ADENOVIRUS ENCODING HUMAN P53 BY COLUMN CHROMATOGRAPHY [J].
HUYGHE, BG ;
LIU, XD ;
SUTJIPTO, S ;
SUGARMAN, BJ ;
HORN, MT ;
SHEPARD, HM ;
SCANDELLA, CJ ;
SHABRAM, P .
HUMAN GENE THERAPY, 1995, 6 (11) :1403-1416
[9]   INHIBITION OF INTERFERON-INDUCIBLE GENE-EXPRESSION BY ADENOVIRUS E1A PROTEINS - BLOCK IN TRANSCRIPTIONAL COMPLEX-FORMATION [J].
KALVAKOLANU, DVR ;
BANDYOPADHYAY, SK ;
HARTER, ML ;
SEN, GC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7459-7463
[10]   GENE-THERAPY - ADENOVIRUS VECTORS [J].
KOZARSKY, KF ;
WILSON, JM .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1993, 3 (03) :499-503