Bioactivities of ricin retained and its immunoreactivity to anti-ricin polyclonal antibodies alleviated through pegylation.
Ricin has long been employed to construct immunotoxins, whose efficacy was often undermined by immunogenicity. Pegylation (modification of proteins with polyethylene glycol, PEG) was one of those recently developed approaches to circumvent immunogenicity of legions of drugs. Herein, pegylation of ricin was found to have barely changed the RNA N-glycosidase activity and protein synthesis inhibiting activity of ricin, but remarkably altered the cytotoxicity of ricin on hepatoma cell line (BEL7404) or the immunoreactivity with polyclonal anti-ricin antibodies. This result suggested that the attached PEG or monomethyloxyl polyethylene glycol (mPEG) groups did not hinder ricin from hydrolyzing ribosomal RNA, but indeed covered some areas on the surface of ricin molecule, including those involved in the interaction with cellular receptors and epitopes recognized by polyclonal antibodies. Pegylation, masking certain epitopes of ricin, might contribute to alleviate the immunogenicity of the toxin. Approach in this work, if applied to thereby constructed immunotoxins, would help improve the prospective efficacy of these toxins.
Hu
Rong-Gui
RG
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 20031, China.
Zhai
Qi-Wei
QW
He
Wen-Jun
WJ
Mei
Ling
L
Liu
Wang-Yi
WY
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D012335:RNA, Ribosomal / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D054788:Ribosome Inactivating Proteins; D012276:Ricin / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000906:Antibodies; D011500:Protein Synthesis Inhibitors; D012335:RNA, Ribosomal; D011092:Polyethylene Glycols; D012276:Ricin; D009699:N-Glycosyl Hydrolases; D054788:Ribosome Inactivating Proteins