Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/13598
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dc.contributor.authorPietersz, Geoffrey Aen
dc.contributor.authorToohey, Ben
dc.contributor.authorMcKenzie, Ian F Cen
dc.date.accessioned2015-05-16T03:28:59Z
dc.date.available2015-05-16T03:28:59Z
dc.date.issued1998-05-16en
dc.identifier.citationJournal of Drug Targeting; 5(2): 109-20en
dc.identifier.govdoc9588867en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/13598en
dc.description.abstractHuman tumor necrosis-alpha (hTNF-alpha) was chemically conjugated to the murine anti-Ly-2.1 T cell antibody using heterobifunctional crosslinking agents SAMSA and SPDP. SDS-PAGE analysis of the affinity purified conjugate consisted mainly of 1:1 and 1:2 (Ly-2.1:TNF) complexes. Conjugated hTNF retained 50% of its cytotoxic activity by the L929 cytolytic assay, with an IC50 = 0.12 ng/ml. hTNF-Ly-2.1 was also cytotoxic to E3 cells (Ly-2.1+ve) with an IC50 = 1.7 microg/ml - 3 times more cytotoxic to these cells than non-conjugated hTNF in vitro. However in vivo hTNF-Ly-2.1 conjugates were more toxic to mice than hTNF. In vivo blood clearance studies in E3 tumor bearing CBF1 mice demonstrated that the half life of the conjugate was 2 hr, compared to 20 min for hTNF. In biodistribution studies, tumor accumulation of 3% was seen for hTNF-Ly-2.1 while for unconjugated hTNF no activity in tumor was detected 24hr post injection. A single dose of hTNF-Ly-2.1 increased the accumulation of 125I-anti-Ly-2.1 by 3 fold compared to controls. However, the antitumor effect of hTNF-Ly-2.1 on E3 cells in vivo was marginal with some tumor growth retardation at day 1-3. The results of these in vitro and in vivo studies on chemically conjugated h-TNF-MoAb will be helpful in the design of novel recombinant fusion proteins for targeting the biologic activity of TNF to tumours.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherAntibodies, Monoclonal.chemistryen
dc.subject.otherCell Lineen
dc.subject.otherDrug Evaluationen
dc.subject.otherHalf-Lifeen
dc.subject.otherHumansen
dc.subject.otherImmunoconjugates.administration & dosage.isolation & purification.pharmacokineticsen
dc.subject.otherMiceen
dc.subject.otherRecombinant Proteins.administration & dosage.pharmacokineticsen
dc.subject.otherThymoma.metabolismen
dc.subject.otherThymus Neoplasms.metabolismen
dc.subject.otherTissue Distributionen
dc.subject.otherTumor Necrosis Factor-alpha.chemistry.pharmacokineticsen
dc.titleIn vitro and in vivo evaluation of human tumor necrosis factor-alpha (hTNFalpha) chemically conjugated to monoclonal antibody.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of drug targetingen
dc.identifier.affiliationThe Austin Research Institute, Austin Hospital, Heidelberg Victoria, Australiaen
dc.identifier.doi10.3109/10611869808995864en
dc.description.pages109-20en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/9588867en
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.cerifentitytypePublications-
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