Arg9-peptide facilitates the internalization of an anti-CEA immunotoxin and potentiates its specific cytotoxicity to target cells.
Arginines-containing membrane translocational signals (MTS), such as Tat(47-57) and VP22(267-300), and synthetic arginine-rich peptides have been reported to be efficient carriers for transporting various types of biomolecules into cytoplasmic and nuclear compartments of living cells. Among those arginines-containing MTS, a 9-mer arginine peptide (Arg9) was proved the most economical and efficient. We fused Arg9-peptide to an anti-CEA (Carcinoembryonic antigen) immunotoxin, PE35/CEA(Fv)/KDEL, at the position between the toxin moiety and the binding moiety. Strong binding and internalization of this fusion protein was observed in all detected cell lines, but little cytotoxicity to the cells that lack the CEA molecules on the cell surface was detected. However, the cytotoxicity besides the binding activity of the fusion protein to specific tumor cells expressing large amount of CEA molecules on the cell surface was improved markedly, indicating that the Arg9-peptide is capable of facilitating the receptor-mediated endocytosis of this immunotoxin, which leads to the increase of the specific cytotoxicity of this immunotoxin.
He
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Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Road Datun, Chaoyang District, Beijing 100101, China.
Yang
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H
Lin
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Q
Huang
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H
D001120:Arginine / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology*; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D001120:Arginine