Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002834547> ?p ?o ?g. }
- W2002834547 endingPage "e0117254" @default.
- W2002834547 startingPage "e0117254" @default.
- W2002834547 abstract "Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety." @default.
- W2002834547 created "2016-06-24" @default.
- W2002834547 creator A5013875777 @default.
- W2002834547 creator A5026414259 @default.
- W2002834547 creator A5027021379 @default.
- W2002834547 creator A5044058894 @default.
- W2002834547 creator A5054905654 @default.
- W2002834547 creator A5064915034 @default.
- W2002834547 creator A5071702929 @default.
- W2002834547 date "2015-02-18" @default.
- W2002834547 modified "2023-09-25" @default.
- W2002834547 title "Hexon Modification to Improve the Activity of Oncolytic Adenovirus Vectors against Neoplastic and Stromal Cells in Pancreatic Cancer" @default.
- W2002834547 cites W1544229812 @default.
- W2002834547 cites W1595155648 @default.
- W2002834547 cites W1833727215 @default.
- W2002834547 cites W1967033604 @default.
- W2002834547 cites W1968180473 @default.
- W2002834547 cites W1968677381 @default.
- W2002834547 cites W1971951822 @default.
- W2002834547 cites W1978183858 @default.
- W2002834547 cites W1979123513 @default.
- W2002834547 cites W1982651102 @default.
- W2002834547 cites W1982805293 @default.
- W2002834547 cites W1985780641 @default.
- W2002834547 cites W1989736806 @default.
- W2002834547 cites W1997392356 @default.
- W2002834547 cites W1998397400 @default.
- W2002834547 cites W1998790582 @default.
- W2002834547 cites W1999753166 @default.
- W2002834547 cites W2011301131 @default.
- W2002834547 cites W2012714016 @default.
- W2002834547 cites W2013093033 @default.
- W2002834547 cites W2016255628 @default.
- W2002834547 cites W2017576006 @default.
- W2002834547 cites W2017614842 @default.
- W2002834547 cites W2022429082 @default.
- W2002834547 cites W2027550738 @default.
- W2002834547 cites W2030504358 @default.
- W2002834547 cites W2032428691 @default.
- W2002834547 cites W2033890530 @default.
- W2002834547 cites W2041625900 @default.
- W2002834547 cites W2043103956 @default.
- W2002834547 cites W2044708576 @default.
- W2002834547 cites W2045578014 @default.
- W2002834547 cites W2046135645 @default.
- W2002834547 cites W2047190365 @default.
- W2002834547 cites W2051758487 @default.
- W2002834547 cites W2052335602 @default.
- W2002834547 cites W2053573489 @default.
- W2002834547 cites W2061448062 @default.
- W2002834547 cites W2063643192 @default.
- W2002834547 cites W2070650369 @default.
- W2002834547 cites W2077541686 @default.
- W2002834547 cites W2079523736 @default.
- W2002834547 cites W2079852426 @default.
- W2002834547 cites W2084192026 @default.
- W2002834547 cites W2089265317 @default.
- W2002834547 cites W2093750998 @default.
- W2002834547 cites W2095615635 @default.
- W2002834547 cites W2098302168 @default.
- W2002834547 cites W2098969570 @default.
- W2002834547 cites W2104416279 @default.
- W2002834547 cites W2112383089 @default.
- W2002834547 cites W2114797146 @default.
- W2002834547 cites W2116071714 @default.
- W2002834547 cites W2135090416 @default.
- W2002834547 cites W2140376045 @default.
- W2002834547 cites W2144624167 @default.
- W2002834547 cites W2149509981 @default.
- W2002834547 cites W2153995704 @default.
- W2002834547 cites W2154021432 @default.
- W2002834547 cites W2155706280 @default.
- W2002834547 cites W2157803722 @default.
- W2002834547 cites W2159716826 @default.
- W2002834547 cites W2165921246 @default.
- W2002834547 cites W2171358858 @default.
- W2002834547 cites W2176798835 @default.
- W2002834547 cites W2314732957 @default.
- W2002834547 cites W2316543256 @default.
- W2002834547 cites W4240210710 @default.
- W2002834547 doi "https://doi.org/10.1371/journal.pone.0117254" @default.
- W2002834547 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4332860" @default.
- W2002834547 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25692292" @default.
- W2002834547 hasPublicationYear "2015" @default.
- W2002834547 type Work @default.
- W2002834547 sameAs 2002834547 @default.
- W2002834547 citedByCount "14" @default.
- W2002834547 countsByYear W20028345472015 @default.
- W2002834547 countsByYear W20028345472016 @default.
- W2002834547 countsByYear W20028345472017 @default.
- W2002834547 countsByYear W20028345472018 @default.
- W2002834547 countsByYear W20028345472021 @default.
- W2002834547 crossrefType "journal-article" @default.
- W2002834547 hasAuthorship W2002834547A5013875777 @default.
- W2002834547 hasAuthorship W2002834547A5026414259 @default.
- W2002834547 hasAuthorship W2002834547A5027021379 @default.
- W2002834547 hasAuthorship W2002834547A5044058894 @default.
- W2002834547 hasAuthorship W2002834547A5054905654 @default.