Please use this identifier to cite or link to this item:
|Title:||In vitro and in vivo evaluation of human tumor necrosis factor-alpha (hTNFalpha) chemically conjugated to monoclonal antibody.||Austin Authors:||Pietersz, Geoffrey A;Toohey, B;McKenzie, Ian F C||Affiliation:||The Austin Research Institute, Austin Hospital, Heidelberg Victoria, Australia||Issue Date:||16-May-1998||Publication information:||Journal of Drug Targeting; 5(2): 109-20||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.||Gov't Doc #:||9588867||URI:||http://ahro.austin.org.au/austinjspui/handle/1/13598||DOI:||10.3109/10611869808995864||URL:||https://pubmed.ncbi.nlm.nih.gov/9588867||Type:||Journal Article||Subjects:||Animals
Immunoconjugates.administration & dosage.isolation & purification.pharmacokinetics
Recombinant Proteins.administration & dosage.pharmacokinetics
Tumor Necrosis Factor-alpha.chemistry.pharmacokinetics
|Appears in Collections:||Journal articles|
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.