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https://ahro.austin.org.au/austinjspui/handle/1/13598
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DC Field | Value | Language |
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dc.contributor.author | Pietersz, Geoffrey A | en |
dc.contributor.author | Toohey, B | en |
dc.contributor.author | McKenzie, Ian F C | en |
dc.date.accessioned | 2015-05-16T03:28:59Z | |
dc.date.available | 2015-05-16T03:28:59Z | |
dc.date.issued | 1998-05-16 | en |
dc.identifier.citation | Journal of Drug Targeting; 5(2): 109-20 | en |
dc.identifier.govdoc | 9588867 | en |
dc.identifier.other | PUBMED | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/13598 | en |
dc.description.abstract | Human 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.iso | en | en |
dc.subject.other | Animals | en |
dc.subject.other | Antibodies, Monoclonal.chemistry | en |
dc.subject.other | Cell Line | en |
dc.subject.other | Drug Evaluation | en |
dc.subject.other | Half-Life | en |
dc.subject.other | Humans | en |
dc.subject.other | Immunoconjugates.administration & dosage.isolation & purification.pharmacokinetics | en |
dc.subject.other | Mice | en |
dc.subject.other | Recombinant Proteins.administration & dosage.pharmacokinetics | en |
dc.subject.other | Thymoma.metabolism | en |
dc.subject.other | Thymus Neoplasms.metabolism | en |
dc.subject.other | Tissue Distribution | en |
dc.subject.other | Tumor Necrosis Factor-alpha.chemistry.pharmacokinetics | en |
dc.title | In vitro and in vivo evaluation of human tumor necrosis factor-alpha (hTNFalpha) chemically conjugated to monoclonal antibody. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Journal of drug targeting | en |
dc.identifier.affiliation | The Austin Research Institute, Austin Hospital, Heidelberg Victoria, Australia | en |
dc.identifier.doi | 10.3109/10611869808995864 | en |
dc.description.pages | 109-20 | en |
dc.relation.url | https://pubmed.ncbi.nlm.nih.gov/9588867 | en |
dc.type.austin | Journal Article | en |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
Appears in Collections: | Journal articles |
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