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Oncolytic viral gene therapy for prostate cancer using two attenuated, replication-competent, genetically engineered
Paul J Cozzi1, Peter B Burke, Amit Bhargav
1The George M O'Brien Urology Research Center, New York, New York, USA. pcozzi@unsw.edu.au
Background:
Attenuated, replication-competent herpes simplex virus mutants offer an exciting new modality in cancer therapy through their ability to selectively replicate within and kill malignant cells with minimal harm to normal tissues.
Methods:
This study investigates the efficacy of two such viruses, G207 and NV1020, in human prostatic carcinoma. In vitro studies were performed on four human prostatic carcinoma cell lines, and in vivo single/multiple dose studies were undertaken on mice by using two human cell types. Tumor volume, histopathology at necropsy, and serum prostate specific antigen (PSA) were used as measures of antiproliferative effect in the in vivo experiments.
Results:
Both viruses were effective in producing cytolytic effects in vitro at various multiplicities of infection in all cell lines tested. Both viruses demonstrated antitumor effects in vivo with a statistically significant decrease in serum PSA and inhibition of growth of both PC-3 and C4-2 subcutaneous xenografts. Tumor-free animals at necropsy were observed in the treated groups but not in control animals.
Conclusion:
These results display impressive activity against human prostate cancer and offer promise for the use of this modality in the future.