Searching for new TNF-α analogs having potential application in cancer therapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-11

AUTHORS

V. Menart, B. Kus, S. Novaković, G. Serša, V. Gaberc-Porekar, V. Harb, S. Miličić, A. Štalc

ABSTRACT

Two new TNF-alpha analogs were prepared and tested for their anti-tumor activity on fibrosarcoma SA-1 tumor model in vivo. In analog LK-801 two histidines (His107His108) were introduced into the surface loop thus enabling efficient purification by metal-affinity chromatography. This analog showed less side effects and can serve as a lead compound to look for other useful mutations. Another analog LK-802 was designed by introduction of additional pair of mutations (Cys95Cys148) into LK-801 in order to prepare disulfide linked TNF trimers. Cytotoxicity on mouse cell line L929 was comparable to TNF-alpha, but effect on tumor growth was quite reduced. Pharmacokinetic study revealed that serum levels of LK-802 were quite low in comparison to native TNF-alpha. This at least partially explains why anti-tumor activity of LK-802 is reduced and also illustrates the problems in designing the analogs with desired in vivo biological properties. More... »

PAGES

r233-r234

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf02346354

DOI

http://dx.doi.org/10.1007/bf02346354

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039506267

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8739350


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