کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1995810 1541483 2007 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cancer selective adenoviruses
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cancer selective adenoviruses
چکیده انگلیسی

Ten years ago Frank McCormick proposed dl1520 as an oncolytic adenovirus. Although great as an inspiration for better oncolytic viruses it was far from a good product. As Onyx-015, it underwent a wish-fulfilling clinical development program seizing the opportunity left by its p53-targeted non-replicative counterpart Ad-p53. Now, facing a skeptical environment, more selective and potent oncolytic adenoviruses await their clinical opportunity. However, advance in key issues remains elusive, such as, selectivity or retargeting at the level of cell receptors to improve pharmacokinetics. Preclinical models and a few clinical data on biodistribution show that only a minimal proportion of the injected dose reaches the tumors after systemic administration. Once in the tumor, the virus must overcome barriers to efficient spread imposed by stroma and immune responses. Arming the oncolytic virus with transgenes is a natural combination of virotherapy and gene therapy strategies. Transgenes that increase virus production or cellular spread may help to overcome these barriers. Cytotoxic transgenes can help to eliminate tumor cells but need to be compatible with efficient virus replication. These challenges require a careful approach to clinical development and a great deal of collaboration to launch clinical tests with a virus backbone that contains intellectual property from multiple sources.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Aspects of Medicine - Volume 28, Issue 1, February 2007, Pages 42–58
نویسندگان
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