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Preclinical Safety ...
Preclinical Safety Assessment of Ad[I/PPT-E1A], a Novel Oncolytic Adenovirus for Prostate Cancer
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Schenk, Ellen (author)
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- Essand, Magnus (author)
- Uppsala universitet,Klinisk immunologi
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Kraaij, Robert (author)
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Adamson, Rachel (author)
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Maitland, Norman J. (author)
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Bangma, Chris H. (author)
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2014
- 2014
- English.
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In: Human Gene Therapy Clinical Development. - : Mary Ann Liebert Inc. - 2324-8637 .- 2324-8645. ; 25:1, s. 7-15
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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