Chemical construction of immunotoxins.
Immunotoxins are chimeric proteins consisting of an antibody linked to a toxin. The antibodies most frequently used for the preparation of immunotoxins are murine monoclonal antibodies belonging to IgG isotype. The most used toxins for the chemical construction of immunotoxins are Ricin toxin A chain in its deglycosylated form and recombinant Pseudomonas endotoxin with the cell-binding domain deleted. The linkage of the antibody to the toxin can be accomplished by chemical methods using reagents that crosslink antibody to toxin. The usual crosslinkers attach disulfide groups into the antibody molecule to form a disulfide bond between the antibody and the toxin. Disulfide bonds are susceptible to reduction in the cytoplasm of the targeted cells thereby releasing the toxin so that it can exert its cytotoxic activity only into the cells (e.g., tumor cells) binding the antibody moiety. This article describes various methods to obtain antibodies and toxins and several procedures for their crosslinking as well as "in vitro" and "in vivo" testing of the immunotoxins efficacy.
Ghetie
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Cancer Immunobiology Center, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8576, USA. Victor.Ghetie@UTSouthwestern.edu
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D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D003432:Cross-Linking Reagents; D004220:Disulfides; D005098:Exotoxins; D006801:Humans; D007074:Immunoglobulin G; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D003432:Cross-Linking Reagents; D004220:Disulfides; D005098:Exotoxins; D007074:Immunoglobulin G; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C024275:pokeweed antiviral protein