Oncolytic herpes simplex virus vector g47delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma.
OBJECTIVE
The use of oncolytic herpes simplex virus type 1 is a promising stategy for cancer treatment. We constructed herpes simplex virus type 1 vector G47Delta by deleting the alpha47 gene and the promoter region of US11 from G207. We now report studies demonstrating the potential of G47Delta as a therapeutic modality for prostate cancer in combination with androgen ablation.


METHODS
The cytopathic activities of G47Delta at low multiplicities of infection was tested in human prostate cancer cell lines LNCaP, PC-3, and DU145 in vitro. Two androgen-dependent mouse s.c. tumor models, murine TRAMP and human HONDA, were used to investigate the in vivo efficacy of G47Delta in combination with androgen ablation.


RESULTS
G47Delta at low multiplicities of infection showed more rapid tumor cell killing than G207 in LNCaP and DU145 in vitro and showed a 22-fold higher virus yield in a single-step growth experiment. In vivo, G47Delta treatment resulted in reduced tumor growth of established s.c. TRAMP and HONDA tumors and inhibited the growth of recurrent HONDA tumors that once regressed by androgen ablation therapy. In both TRAMP and HONDA tumor xenografts, the combination therapy of G47Delta with androgen ablation led to significantly enhanced inhibition of the tumor growth and prolonged survival.


CONCLUSIONS
These results suggest that oncolytic virus therapy with G47Delta can be usefully combined with androgen ablation therapy for the treatment of prostate cancer.
Fukuhara
Hiroshi
H
Molecular Neurosurgery Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.
Martuza
Robert L
RL
Rabkin
Samuel D
SD
Ito
Yoshikazu
Y
Todo
Tomoki
T
D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D050504:Oncolytic Viruses / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D012008:Recurrence; D018139:Simplexvirus / Q000235:genetics*; D013997:Time Factors
D000728:Androgens