Linked Life Data

8912858

Source:http://linkedlifedata.com/resource/pubmed/id/8912858

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1997-1-7
pubmed:abstractText
A marked effect of charge modification on the uptake and phototoxicity of a photoimmunoconjugate (PIC) was demonstrated. A site-specific conjugation strategy was developed to attach the photosensitizer chlorin(e6) (c(e6)) to the F(ab')2 fragment of the murine antiovarian cancer monoclonal antibody OC125. Poly-L-lysine linkers carrying c(e6) with a cationic charge or by polysuccinylation with an anionic charge were used and covalently attached to partially reduced antibody via a heterobifunctional reagent. PICs were purified by column chromatography and were also radiolabeled with 125I. PIC binding and uptake were studied with a human ovarian cancer cell line, NIH-OVCAR-5, and a nonantigen-expressing colon cancer cell line, SW1116, and the data were compared with the binding and uptake of nonspecific rabbit IgG PICs. PICs with both cationic and anionic charges preserved antigen binding as shown by competition studies with native antibody, but the cationic PIC had up to 17 times higher cellular uptake of c(e6), probably due to enhanced internalization. The ratio of c(e6) to 125I retained by the cells varied with the likelihood of internalization and lysosomal degradation. The phototoxicity of the PICs generally varied with their uptake, but a correlation was found between lysosomal hydrolysis as measured by an increased cellular ratio of c(e6):125I and increased relative phototoxicity. These data suggest cationic PICs may have advantages for photoimmunotherapy of disseminated intracavity cancer following local administration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5205-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Effect of charge on the interaction of site-specific photoimmunoconjugates with human ovarian cancer cells.
pubmed:affiliation
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.