Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-25
pubmed:abstractText
The use of adenovirus (Ad) vectors for cancer gene therapy applications is currently limited by several factors, including broad Ad tropism associated with the widespread expression of coxsackievirus and adenovirus receptor (CAR) in normal human tissues, as well as limited levels of CAR in tumor cells. To target Ad to relevant cell types, we have proposed using soluble CAR (sCAR) ectodomain fused with a ligand to block CAR-dependent native tropism and to simultaneously achieve infection through a novel receptor overexpressed in target cells. To confer Ad targeting capability on cancer cells expressing the c-erbB-2/HER-2/neu oncogene, we engineered a bispecific adapter protein, sCARfC6.5, that consisted of sCAR, phage T4 fibritin polypeptide, and C6.5 single-chain fragment variable (scFv) against c-erbB-2 oncoprotein. Incorporation of fibritin polypeptide provided trimerization of sCAR fusion proteins that, compared with monomeric sCAR protein, resulted in augmented affinity to Ad fiber knob domain and in increased ability to block CAR-dependent Ad infection. We demonstrated that sCARfC6.5 protein binds to cellular c-erbB-2 oncoprotein and mediates efficient Ad targeting via a CAR-independent pathway. As illustrated in cancer cell lines that overexpress c-erbB-2, targeted Ad, complexed with sCARfC6.5 adapter protein, provided from 1.5- to 17-fold enhancement of gene transfer compared with Ad alone and up to 130-fold increase in comparison with untargeted Ad complexed with sCARf control protein. The use of recombinant trimeric sCAR-scFv adapter proteins may augment Ad vector potency for targeting cancer cell types.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-16
pubmed:dateRevised
2011-7-1
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Adenovirus targeting to c-erbB-2 oncoprotein by single-chain antibody fused to trimeric form of adenovirus receptor ectodomain.
pubmed:affiliation
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, 35294-3300, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.