Treatment of prostate cancer with Ad5/3Delta24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo.

Abstract:

:Hormone refractory metastatic prostate cancer is a deadly disease that currently lacks curative treatments. Conditionally replicating adenoviruses (CRAds) are promising new agents against cancer due to their innate capability to cause oncolysis of tumor cells. Their antitumor effect is determined in part by their capacity for infecting cancer cells. However, the respective primary receptor, the coxsackie-adenovirus receptor (CAR), is variably expressed in many cancer types. We created Ad5/3Delta24hCG, a novel CRAd retargeted to the adenovirus serotype 3 receptor, which has been reported to be highly expressed in tumors. Furthermore, we added a transgene for the beta-chain of human chorionic gonadotropin (hCGbeta), whose expression was tightly coupled to virus replication. Ad5/3Delta24hCG was found effective in killing prostate cancer cells, and oncolysis was seen in concordance with hCGbeta production. In a s.c. in vivo model of hormone refractory prostate cancer, Ad5/3Delta24hCG treatment resulted in statistically significant tumor growth inhibition. Moreover, i.v. injection of Ad5/3Delta24hCG prolonged the survival of mice with hormone refractory prostate cancer metastatic to the lung. Detection of hCGbeta in serum samples confirmed viral replication in vivo. Infection of human clinical samples of cancerous and normal prostatic tissue resulted in effective hCGbeta production in cancer tissue, whereas it remained low in nonmalignant tissue, suggesting cancer-specific replication. These results suggest that Ad5/3Delta24hCG is a potent virus for the treatment of hormone refractory prostate cancer in vitro and in vivo. These preclinical data set the stage for translation into clinical studies.

journal_name

Mol Cancer Ther

authors

Rajecki M,Kanerva A,Stenman UH,Tenhunen M,Kangasniemi L,Särkioja M,Ala-Opas MY,Alfthan H,Sankila A,Rintala E,Desmond RA,Hakkarainen T,Hemminki A

doi

10.1158/1535-7163.MCT-06-0403

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

742-51

issue

2

eissn

1535-7163

issn

1538-8514

pii

6/2/742

journal_volume

6

pub_type

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