Linked Life Data

15958576

Source:http://linkedlifedata.com/resource/pubmed/id/15958576

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-6-16
pubmed:abstractText
Targeting tumor-associated vascular endothelium by replication-competent viral vectors is a promising strategy for cancer gene therapy. Here we describe the development of a viral vector based on the Edmonston vaccine strain of measles virus targeted to integrin alpha(v)beta3, which is expressed abundantly on activated but not quiescent vascular endothelium. We displayed a disintegrin, M28L echistatin that binds with a high affinity to integrin alpha(v)beta3 on the COOH terminus of the viral attachment (H) protein and rescued the replication-competent recombinant virus by reverse genetics. The new targeted virus was named measles virus echistatin vector (MV-ERV). Its native binding to CD46 was purposefully retained to allow virus infection of tumor cells expressing this receptor. MV-ERV correctly displayed echistatin on the outer surface of its envelope and produced interesting ring formation phenomena due to cell detachment upon infection of susceptible Vero cells in vitro. MV-ERV grew to 10(6) plaque-forming units/mL, slightly lower than the parental Edmonston strain of measles virus (MV-Edm), but it selectively infected Chinese hamster ovary cells expressing integrin alpha(v)beta3. It also selectively infected both bovine and human endothelial cells on matrigels and unlike MV-Edm, MV-ERV infected newly formed blood vessels in chorioallantoic membrane assays. In animal models, MV-ERV but not the control MV-Edm caused the regression of s.c. xenografts of resistant multiple myeloma tumors (MM1) in severe combined immunodeficient mice. The tumors were either completely eradicated or their growth was significantly retarded. The specificity, potency, and feasibility of MV-ERV infection clearly show the potential use of MV-ERV in gene therapy for targeting tumor-associated vasculature for the treatment of solid tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5292-300
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15958576-Amino Acid Sequence, pubmed-meshheading:15958576-Animals, pubmed-meshheading:15958576-Antigens, CD, pubmed-meshheading:15958576-Antigens, CD46, pubmed-meshheading:15958576-CHO Cells, pubmed-meshheading:15958576-Cattle, pubmed-meshheading:15958576-Cercopithecus aethiops, pubmed-meshheading:15958576-Chick Embryo, pubmed-meshheading:15958576-Cricetinae, pubmed-meshheading:15958576-Endothelial Cells, pubmed-meshheading:15958576-Gene Therapy, pubmed-meshheading:15958576-Genetic Vectors, pubmed-meshheading:15958576-Humans, pubmed-meshheading:15958576-Integrin alphaVbeta3, pubmed-meshheading:15958576-Measles virus, pubmed-meshheading:15958576-Membrane Glycoproteins, pubmed-meshheading:15958576-Mice, pubmed-meshheading:15958576-Mice, SCID, pubmed-meshheading:15958576-Molecular Sequence Data, pubmed-meshheading:15958576-Multiple Myeloma, pubmed-meshheading:15958576-Neovascularization, Pathologic, pubmed-meshheading:15958576-Peptides, pubmed-meshheading:15958576-Transfection, pubmed-meshheading:15958576-Vero Cells, pubmed-meshheading:15958576-Viral Proteins
pubmed:year
2005
pubmed:articleTitle
Targeted measles virus vector displaying echistatin infects endothelial cells via alpha(v)beta3 and leads to tumor regression.
pubmed:affiliation
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural