Treatment of ovarian cancer with a tropism modified oncolytic adenovirus.
Ad5-Delta 24RGD is an adenovirus that is selectively replication competent in cells defective in the Rb/p16 pathway, such as ovarian cancer cells. The fiber of Ad5-Delta 24RGD contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of cancer cells. Oncolysis of cell lines was similar to that of a wild-type control, and replication in primary tumor material was shown using a novel three-dimensional spheroid model. Finally, an orthotopic murine model of peritoneally disseminated ovarian cancer was used to test i.p. administration to tumor-bearing animals. Injection of the agent resulted in eradication of i.p. disease, whereas control animals expired (P < 0.0001). These results suggest that Ad5-Delta 24RGD could be useful for treatment of ovarian cancer in humans.
Bauerschmitz
Gerd J
GJ
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
Lam
John T
JT
Kanerva
Anna
A
Suzuki
Kaori
K
Nettelbeck
Dirk M
DM
Dmitriev
Igor
I
Krasnykh
Victor
V
Mikheeva
Galina V
GV
Barnes
Mack N
MN
Alvarez
Ronald D
RD
Dall
Peter
P
Alemany
Ramon
R
Curiel
David T
DT
Hemminki
Akseli
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D015316:Genetic Therapy; D051379:Mice; D016513:Mice, SCID; D009842:Oligopeptides / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000628:therapy*; D018874:Spheroids, Cellular; D014779:Virus Replication
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid