Linked Life Data

16314943

Source:http://linkedlifedata.com/resource/pubmed/id/16314943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-5-15
pubmed:abstractText
DTAT13, a novel recombinant bispecific immunotoxin (IT) consisting of truncated diphtheria toxin, an amino-terminal (AT) fragment of the urokinase-type plasminogen activator (uPa), and a fragment of human IL-13 was assembled in order to target receptors on glioblastoma multiforme (GBM) and its associated neovasculature. Previous in vitro studies confirmed the efficacy of DTAT13 against various GBM cell lines expressing both IL-13 receptor or uPA receptor, and previous in vivo testing demonstrated the efficacy of DTAT13 in significantly inhibiting a range of xenograft tumors and showed that DTAT13 was 160- and 8-fold less toxic to the parental fusion IT, DTAT and DTIL13, respectively. To further understand the properties of DTAT13, pharmacokinetic/biodistribution experiments were performed. Binding analysis revealed that the IL-13 domain functioned independently of the uPA domain and that the K (d) for each binding domain was essentially the same as that of DTIL13 and DTAT. Flow cytometry studies indicated that DTAT13 bound better than DTAT or DTIL13. Analysis of the rate of protein synthesis inhibition in U87 MG cells by DTAT13 compared to DTAT revealed a faster rate of inhibition with DTAT13 compared to DTAT. The rate of protein synthesis inhibition of DTAT13 was identical to that of DTIL13 in U373 MG cells. Intracranial biodistribution studies revealed that DTAT13 was able to cross to the contralateral hemisphere unlike DTIL13 but similar to DTAT. These studies show that DTAT13 has properties encompassing those of both DTIL13 and DTAT and warrants further consideration for clinical development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0167-594X
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-66
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Immunotoxin pharmacokinetics: a comparison of the anti-glioblastoma bi-specific fusion protein (DTAT13) to DTAT and DTIL13.
pubmed:affiliation
Department of Neurosurgery, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural