Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer: expression of coxsackie-adenovirus receptor and integrins alphavbeta3 and alphavbeta5.
OBJECTIVE
Ten patients with recurrent ovarian cancer received a combined treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (GT), and systemic application of acyclovir or valacyclovir and topotecan. Biopsies were taken at the time of secondary debulking about 1 month after the application of GT and chemotherapy and were analyzed for expression of coxsackie-adenovirus receptor (CAR) and integrins alphavbeta3 and alphavbeta5 with respect to treatment response.


METHODS
Treatment modalities and study design have been described recently. Immunohistochemistry was used to visualize expression of CAR and integrins alphavbeta3 and alphavbeta5 in tumor samples taken before and after application of GT.


RESULTS
Before GT six of ten patients presented with CAR-positive and four with CAR-negative tumors. After GT all tumors showed CAR expression. Integrin alphavbeta3 was found in all tumors before and after GT. Expression of integrin alphavbeta5 was seen in eight of ten tumor samples before GT and in all samples after GT.


CONCLUSIONS
Despite the importance of CAR and integrin expression for successful adenovirus internalization, other cell surface receptors might be involved in this process. It is too early to decide whether expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells are appropriate additional inclusion criteria for the enrollment of patients in GT trials. Further research is necessary to evaluate the effect of GT plus chemotherapy on CAR and integrin expression.
Hasenburg
A
A
Department of Obstetrics and Gynecology, University Medical Center, Hugstetter Strasse 55, 79106 Freiburg/Brsg., Germany. ahasenb@frk.ukl.uni-freiburg.de
Fischer
D-C
DC
Tong
X-W
XW
Rojas-Martinez
A
A
Kaufman
R H
RH
Ramzy
I
I
Kohlberger
P
P
Orlowska-Volk
M
M
Aguilar-Cordova
E
E
Kieback
D G
DG
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004770:Enterovirus / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D019030:Receptors, Vitronectin / Q000235:genetics*; D012008:Recurrence; D024162:Second-Look Surgery; D013937:Thymidine Kinase / Q000235:genetics*
D016023:Integrins; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D013937:Thymidine Kinase