期刊
GENE THERAPY
卷 17, 期 6, 页码 805-810出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2010.20
关键词
HSV; TRAMP; virotherapy; cancer therapy
类别
资金
- DOD [W81XWH-04-1-0254]
- NIH [R01 CA102139]
Prostate cancer is one of the most prevalent cancers in men. Replication-competent oncolytic herpes simplex virus (oHSV) vectors are a powerful antitumor therapy that can exert at least two effects: direct cytocidal activity that selectively kills cancer cells and induction of antitumor immunity. In addition, oHSV vectors can also function as a platform to deliver transgenes of interest. In these studies, we have examined the expression of a xenogeneic homologue of the prostate cancer antigen, prostatic acid phosphatase (PAP), with the goal of enhancing virotherapy against PAP-expressing tumors. PAP has already been used for cancer vaccination in patients with prostate cancer. Here we show that treatment with oHSV bP Delta 6 expressing xenogeneic human PAP (hPAP) significantly reduces tumor growth and increases survival of C57/BL6 mice bearing mouse TRAMP-C2 prostate tumors, whereas expression of syngeneic mouse PAP (mPAP) from the same oHSV vector did not enhance antitumor activity. Treatment of mice bearing metastatic TRAMP-C2 lung tumors with oHSV-expressing hPAP resulted in fewer tumor nodules. To our knowledge, this is the first report of oncolytic viruses being used to express xenoantigens. These data lend support to the concept of combining oncolytic and immunogenic therapies as a way to improve therapy of metastatic prostate cancer. Gene Therapy (2010) 17, 805-810; doi: 10.1038/gt.2010.20; published online 11 March 2010
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