Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect

被引:80
作者
Fu, XP
Tao, L
Jin, AW
Vile, R
Brenner, MK
Zhang, XL [1 ]
机构
[1] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[2] Mayo Clin, Program Mol Med, Rochester, MN 55905 USA
关键词
oncolytic; herpes simplex virus; late viral promoter; fusogenic membrane glycoprotein; liver cancer;
D O I
10.1016/S1525-0016(03)00092-3
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
Oncolytic viruses have shown considerable promise in the treatment of solid tumors, but their potency must be improved if their full clinical potential is to be realized. We inserted the gene encoding a truncated form of the gibbon ape leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. Furthermore, by controlling GALV.fus expression through a strict late viral promoter, whose activity depends on the initiation of viral DNA replication, we were able to express this glycoprotein in tumor cells but not in normal nondividing cells. It will be of interest to confirm whether functional expression of a strong fusogenic gene by an oncolytic herpes simplex virus enhances viral antitumor activity without increasing its toxicity.
引用
收藏
页码:748 / 754
页数:7
相关论文
共 27 条
[1]  
Bateman A, 2000, CANCER RES, V60, P1492
[2]   Enhancement of gene therapy specificity for diffuse colon carcinoma liver metastases with recombinant herpes simplex virus [J].
Carroll, NM ;
Chiocca, EA ;
Takahashi, K ;
Tanabe, KK .
ANNALS OF SURGERY, 1996, 224 (03) :323-329
[3]  
Coukos G, 1999, CLIN CANCER RES, V5, P1523
[4]   A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy [J].
Diaz, RM ;
Bateman, A ;
Emiliusen, L ;
Fielding, A ;
Trono, D ;
Russell, SJ ;
Vile, RG .
GENE THERAPY, 2000, 7 (19) :1656-1663
[5]   A hyperfusogenic gibbon ape leukemia envelope glycoprotein: Targeting of a cytotoxic gene by ligand display [J].
Fielding, AK ;
Chapel-Fernandes, S ;
Chadwick, MP ;
Bullough, FJ ;
Cosset, FL ;
Russell, SJ .
HUMAN GENE THERAPY, 2000, 11 (06) :817-826
[6]  
Fu XP, 2002, CANCER RES, V62, P2306
[7]   MUTATIONAL ANALYSIS OF THE HERPES-SIMPLEX VIRUS TYPE-1 STRICT LATE UL38 PROMOTER LEADER REVEALS 2 REGIONS CRITICAL IN TRANSCRIPTIONAL REGULATION [J].
GUZOWSKI, JF ;
WAGNER, EK .
JOURNAL OF VIROLOGY, 1993, 67 (09) :5098-5108
[8]  
Higuchi H, 2000, CANCER RES, V60, P6396
[9]   Functional analysis of the cytoplasmic tail of Moloney murine leukemia virus envelope protein [J].
Januszeski, MM ;
Cannon, PM ;
Chen, DG ;
Rozenberg, Y ;
Anderson, WF .
JOURNAL OF VIROLOGY, 1997, 71 (05) :3613-3619
[10]   Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015):: results of Phase I and II trials [J].
Kirn, D .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2001, 1 (03) :525-538