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Preclinical Safety Assessment of Ad[I/PPT-E1A], a Novel Oncolytic Adenovirus for Prostate Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2014 (English)In: Human Gene Therapy Clinical Development, ISSN 2324-8637, Vol. 25, no 1, 7-15 p.Article in journal (Refereed) Published
Abstract [en]

Prostate cancer is the most common malignancy in the Western world. Patients can be cured only when the tumor has not metastasized outside the prostate. However, treatment with curative intent fails in a significant number of men, often resulting in untreatable progressive disease with a fatal outcome. Oncolytic adenovirus therapy may be a promising adjuvant treatment to reduce local failure or the outgrowth of micrometastatic disease. Within the European gene therapy consortium GIANT, we have developed a novel prostate-specific oncolytic adenovirus: Ad[I/PPT-E1A]. This adenovirus specifically kills prostate cells via prostate-specific replication. This article describes the clinical development of Ad[I/PPT-E1A] with particular reference to the preclinical safety assessment of this novel virus. The preclinical safety assessment involved an efficacy study in a human orthotopic xenograft mouse model, a specificity study in human primary cells, and a toxicity study in normal mice. These studies confirmed that Ad[I/PPT-E1A] efficiently kills prostate tumor cells in vivo, is not harmful to other organs, and is well tolerated in mice after systemic delivery. The safety, as well as the immunological effects of Ad[I/PPT-E1A] as a local adjuvant therapy, will now be studied in a phase I dose-escalating trial in patients with localized prostate cancer who are scheduled for curative radical prostatectomy and can be used as an updated paradigm for similar therapeutic viruses.

Place, publisher, year, edition, pages
2014. Vol. 25, no 1, 7-15 p.
National Category
Cancer and Oncology Urology and Nephrology
URN: urn:nbn:se:uu:diva-238983DOI: 10.1089/humc.2013.181ISI: 000344476100002PubMedID: 24649837OAI: oai:DiVA.org:uu-238983DiVA: diva2:773040
Available from: 2014-12-18 Created: 2014-12-17 Last updated: 2014-12-18Bibliographically approved

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