Studies on biological properties of hTNFα multi-site mutants / 细胞与分子免疫学杂志
Chinese Journal of Cellular and Molecular Immunology
; (12): 5-7,15, 2001.
Article
en Zh
| WPRIM
| ID: wpr-625056
Biblioteca responsable:
WPRO
ABSTRACT
im To study the structure-function relationship of hTNFα . Methods We compared the cytotoxicity, receptor binding ability and toxicity in animal body of wild type(wt)hTNFα with its mutants including R2K-, N30S-, R32W-, L157F-hTNFα , and two multi-site mutants(R32W-L157F-hTNFα and R2K-N30S-R32W-L157F-hTNFα ). Results We found that the two multi-site mutants remained similar cytotoxicity to several human tumor cell lines as wild type hTNFα . However, their cytotoxicity to L929 cells were decreased sharply as compared with those of wt hTNFα . The two multi-site hTNFα mutants had lower binding activity with hTR75 than hTR55. We also found that compared with the wild type, the LD50 of the mutant R32W-L157F-hTNFα was decreased about 300 fold and the dose of mutant R2K-N30S-R32W-L157F-hTNFα resulted in 30% death was 700 folds lower than LD50 of wt hTNFα . To certify the systematic toxicity of the mutant R2K-N30S-R32W-L157F-hTNFα , we assayed its toxicity to monkeys and found that its systematic toxicity was lower than that of wt hTNFα. Conclusion A 4-site mutants(R2k-N30S-R32W-L157F-hTNFα )of hTNFα is obtained, which the mutant may possess potential application value in clinical therapy.
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Índice:
WPRIM
Idioma:
Zh
Revista:
Chinese Journal of Cellular and Molecular Immunology
Año:
2001
Tipo del documento:
Article