Safety evaluation and pharmacokinetics of a novel human tumor necrosis factor-alpha exhibited a higher antitumor activity and a lower systemic toxicity.
Safety evaluation and pharmacokinetics of a novel human tumor necrosis factor-alpha exhibited a higher antitumor activity and a lower systemic toxicity.
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DOI：
10.1097/cad.0b013e328333d5ce
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发表时间：
2010-03
影响因子：
2.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li M;Qin X;Xue X;Zhang C;Yan Z;Han W;Komarck C;Wang TD;Zhang Y
We have previously prepared a prokaryotic expressed TNF-α mutant which exhibited a higher anti-tumor activity and a lower systemic toxicity compared with that of wild type TNF-α in both syngeneic murine tumor models and human tumor xenografts models. For its clinical use as an anti-tumor agent, we evaluate repeated dose toxicity, anaphylaxis, genetic toxicity, pharmacokinetic and metabolism in different animals according to the criteria for biological Investigational New Drug (IND) application. It was found to be safe at a dose of 4×106 IU/kg/day for 60 days after administration in rhesus monkeys but the TNF-α antibody level and liver toxicity needed to be monitored. No systemic anaphylaxis or genetic toxicity were found and the pharmacokinetic characteristics of the rmhTNF-α were suited for clinical use. Over 96.3% of rmhTNF-α could be reclaimed from the urine and feces in 24 hours after administration, which indicated the main excretion route. The results proved the characteristics of this rmhTNF-α satisfied clinical trial requirements. The related positive clinical trial results will be reported in future. This study of novel rmhTNF-α is of considerable importance, not only given the proven usefulness of TNF-α local application therapies under ILP (Isolated Limp Perfusion) and IHP (Isolated Hepatic Perfusion) conditions for selected indications, but also implicated for systemic application of TNF-α.
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影响因子：
11.4
作者：
BARBARA, JAJ;SMITH, WB;LOPEZ, AF
通讯作者：
LOPEZ, AF
影响因子：
2.5
作者：
Cherix, Stephane;Speiser, Melanie;Leyvraz, Pierre-Francois
通讯作者：
Leyvraz, Pierre-Francois
DOI：
10.1016/0006-291x(87)90923-5
发表时间：
1987-10-29
影响因子：
3.1
作者：
SOMA, GI;KITAHARA, N;MIZUNO, D
通讯作者：
MIZUNO, D
影响因子：
4
作者：
Depuydt, B;Van Loo, G;Declercq, W
通讯作者：
Declercq, W
影响因子：
56.9
作者：
SUGARMAN, BJ;AGGARWAL, BB;SHEPARD, HM
通讯作者：
SHEPARD, HM