FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567162800> ?p ?o ?g. }

• W1567162800 endingPage "842" @default.
• W1567162800 startingPage "841" @default.
• W1567162800 abstract "A substantial challenge for gene therapists is achieving sufficient levels of gene delivery in target tissue to elicit an acceptable therapeutic effect. Localized gene transfer in vivo is often not a viable or even preferred option, for example, in cancer gene therapy targeted to disseminated metastases. In such scenarios, injection of the therapeutic vector into the bloodstream is the only viable route but is compromised by the relatively poor tumor targeting capacity of currently available vectors. The development and optimization of more effective vectors is a key area of development in the cancer gene therapy field. Of particular interest are systems based on oncolytic measles virus, herpesvirus, and adenovirus (Ad). In this issue of Molecular Therapy, Mocanu and colleagues1Mocanu JD Yip KW Alajez NM Shi W Li J-H Lunt SJ et al.Imaging the modulation of adenoviral kinetics and biodistribution for cancer gene therapy.Mol Ther. 2007; 15: 921-929Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar use longitudinal bioluminescence imaging to define the transduction kinetics of adenoviruses. Elegant use of imaging defined tumor and off-target transduction mediated by adenoviruses transcriptionally controlled for Epstein-Barr virus (EBV)–positive xenografts in SCID mice after intravenous delivery. As expected, tumor transgene levels were higher using EBV-targeted transcriptional control than with the relatively weak but “constitutive” simian virus 40 promoter. Because liver transduction was significant, the authors pursued several pharmacological interventions to improve tumor-specific virus control. STI571 (Glivec) administration reduced tumor interstitial fluid pressure, diminished activation of the platelet-derived growth factor–β receptor, and, interestingly, improved the tumor-to-liver transduction ratio. Hence, combinatorial approaches may offer improved tumor targeting by Ad. Unfortunately, the effect of STI571 on tumor burden after intravascular administration of conditionally replicating EBV-targeted adenoviruses was not evaluated in this study. The authors chose intratumoral injection of virus in conjunction with STI571 to evaluate efficacy, although STI571 did not modulate tumor growth despite enhancing initial tumor transgene levels. In spite of its shortcomings, this study highlights several important issues. First, instilling transcriptional control of Ad vectors is a logical strategy for improving selectivity. However, transcriptional control does not influence Ad biodistribution per se. Assessment of vector biodistribution is critical in defining site-selective targeting of any gene-delivery system. For adenoviruses this should not be accomplished solely by assessment of vector and transgene at late time points but should also involve assessment of virus-uptake kinetics at very early time points after injection, ideally involving systematic analysis of liver, splenic, and target-tissue uptake. Because Ad interaction with the host is highly dynamic, early analysis will provide essential information on the possibility that any modifications in protocol design could have an impact on native vector tropism and on target-tissue homing. In the case of oncolytic therapy this is particularly relevant in that off-target vector replication may be a critical determinant of therapeutic index. Second, marginal improvements in Ad targeting, at either the transductional or transcriptional level, or indeed both, are unlikely to have any significant impact on efficacy. Third, it is imperative to determine the effect of drug interventions on transcriptional activity of promoters, because this will influence interpretation and potential translation aspects of any combinatorial approach to the clinic. Several other approaches exist to improve Ad-mediated delivery to tumors after intravascular injection. Targeting strategies include fiber/serotype swapping, as well as use of peptide- and antibody-based targeting regimens (see review2Nicklin SA Wu E Nemerow G Baker AH The influence of adenovirus fiber structure and function on vector development for gene therapy.Mol Ther. 2005; 12: 384-393Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). Ascertaining the most effective targeting regimen is difficult and requires careful consideration. Thus far, switching to CD46-utilizing adenoviruses offers a high-affinity alternative virus–receptor interaction,3Gaggar A Shayakhmetov DM Lieber A CD46 is a cellular receptor for group B adenoviruses.Nat Med. 2003; 9: 1-5Crossref Scopus (626) Google Scholar potentially allowing the targeting of CD46-overexpressing tumors in vivo. At present there is an incomplete understanding of the complex mechanisms that govern in vivo Ad biodistribution when delivered via the intravascular route. Important aspects include blood-cell interactions, binding of Ad to plasma proteins, and the affinity of interaction with cellular receptor mechanism(s) at target sites. Approaches to understanding and modifying these interactions may further improve tumor delivery. Hence, highly efficient and selective tumor targeting via intravascular injection remains a formidable challenge. Approaches to improving delivery with pharmacological enhancement of tumor-virus uptake with additional transcriptional control, as documented by Mocanu et al.,1Mocanu JD Yip KW Alajez NM Shi W Li J-H Lunt SJ et al.Imaging the modulation of adenoviral kinetics and biodistribution for cancer gene therapy.Mol Ther. 2007; 15: 921-929Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar perhaps in conjunction with vector engineering strategies, may further improve the efficacy of cancer gene therapy." @default.
• W1567162800 created "2016-06-24" @default.
• W1567162800 creator A5074705058 @default.
• W1567162800 date "2007-05-01" @default.
• W1567162800 modified "2023-09-23" @default.
• W1567162800 title "Shedding Light on Tumor Targeting by Adenovirus" @default.
• W1567162800 cites W1965401351 @default.
• W1567162800 cites W1981755236 @default.
• W1567162800 cites W2163708786 @default.
• W1567162800 doi "https://doi.org/10.1038/sj.mt.6300158" @default.
• W1567162800 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17446868" @default.
• W1567162800 hasPublicationYear "2007" @default.
• W1567162800 type Work @default.
• W1567162800 sameAs 1567162800 @default.
• W1567162800 citedByCount "2" @default.
• W1567162800 crossrefType "journal-article" @default.
• W1567162800 hasAuthorship W1567162800A5074705058 @default.
• W1567162800 hasBestOaLocation W15671628001 @default.
• W1567162800 hasConcept C102230213 @default.
• W1567162800 hasConcept C104317684 @default.
• W1567162800 hasConcept C111335760 @default.
• W1567162800 hasConcept C111599444 @default.
• W1567162800 hasConcept C121608353 @default.
• W1567162800 hasConcept C135983454 @default.
• W1567162800 hasConcept C15152581 @default.
• W1567162800 hasConcept C159047783 @default.
• W1567162800 hasConcept C161997846 @default.
• W1567162800 hasConcept C207001950 @default.
• W1567162800 hasConcept C22070199 @default.
• W1567162800 hasConcept C2522874641 @default.
• W1567162800 hasConcept C2776438120 @default.
• W1567162800 hasConcept C2777283488 @default.
• W1567162800 hasConcept C2777807558 @default.
• W1567162800 hasConcept C2778199166 @default.
• W1567162800 hasConcept C32470452 @default.
• W1567162800 hasConcept C40767141 @default.
• W1567162800 hasConcept C49744831 @default.
• W1567162800 hasConcept C502942594 @default.
• W1567162800 hasConcept C54009773 @default.
• W1567162800 hasConcept C54355233 @default.
• W1567162800 hasConcept C55493867 @default.
• W1567162800 hasConcept C71924100 @default.
• W1567162800 hasConcept C82210918 @default.
• W1567162800 hasConcept C86803240 @default.
• W1567162800 hasConceptScore W1567162800C102230213 @default.
• W1567162800 hasConceptScore W1567162800C104317684 @default.
• W1567162800 hasConceptScore W1567162800C111335760 @default.
• W1567162800 hasConceptScore W1567162800C111599444 @default.
• W1567162800 hasConceptScore W1567162800C121608353 @default.
• W1567162800 hasConceptScore W1567162800C135983454 @default.
• W1567162800 hasConceptScore W1567162800C15152581 @default.
• W1567162800 hasConceptScore W1567162800C159047783 @default.
• W1567162800 hasConceptScore W1567162800C161997846 @default.
• W1567162800 hasConceptScore W1567162800C207001950 @default.
• W1567162800 hasConceptScore W1567162800C22070199 @default.
• W1567162800 hasConceptScore W1567162800C2522874641 @default.
• W1567162800 hasConceptScore W1567162800C2776438120 @default.
• W1567162800 hasConceptScore W1567162800C2777283488 @default.
• W1567162800 hasConceptScore W1567162800C2777807558 @default.
• W1567162800 hasConceptScore W1567162800C2778199166 @default.
• W1567162800 hasConceptScore W1567162800C32470452 @default.
• W1567162800 hasConceptScore W1567162800C40767141 @default.
• W1567162800 hasConceptScore W1567162800C49744831 @default.
• W1567162800 hasConceptScore W1567162800C502942594 @default.
• W1567162800 hasConceptScore W1567162800C54009773 @default.
• W1567162800 hasConceptScore W1567162800C54355233 @default.
• W1567162800 hasConceptScore W1567162800C55493867 @default.
• W1567162800 hasConceptScore W1567162800C71924100 @default.
• W1567162800 hasConceptScore W1567162800C82210918 @default.
• W1567162800 hasConceptScore W1567162800C86803240 @default.
• W1567162800 hasIssue "5" @default.
• W1567162800 hasLocation W15671628001 @default.
• W1567162800 hasLocation W15671628002 @default.
• W1567162800 hasOpenAccess W1567162800 @default.
• W1567162800 hasPrimaryLocation W15671628001 @default.
• W1567162800 hasRelatedWork W1861506798 @default.
• W1567162800 hasRelatedWork W1971831772 @default.
• W1567162800 hasRelatedWork W1998321926 @default.
• W1567162800 hasRelatedWork W2000407190 @default.
• W1567162800 hasRelatedWork W2027834277 @default.
• W1567162800 hasRelatedWork W2062997542 @default.
• W1567162800 hasRelatedWork W2079316258 @default.
• W1567162800 hasRelatedWork W2591985424 @default.
• W1567162800 hasRelatedWork W40095188 @default.
• W1567162800 hasRelatedWork W4379231518 @default.
• W1567162800 hasVolume "15" @default.
• W1567162800 isParatext "false" @default.
• W1567162800 isRetracted "false" @default.
• W1567162800 magId "1567162800" @default.
• W1567162800 workType "article" @default.