The history of monoclonal antibody development – Progress, remaining challenges and future innovations

Liu, Justin K.H.

Monoclonal antibodies can also be modified in order to have additional effects as well. Teicher and Chari discuss the possibilities of conjugated antibodies which involves coupling effector molecules to monoclonal antibodies (e.g. plant/bacterial toxins, enzymes, radionuclides, cytotoxic drugs, etc.) [26] . Chemical coupling of effector molecules to monoclonal antibodies is usually done with the aid of chemical ligands (i.e. joining molecules). Sites for coupling on the monoclonal antibodies usually include: thiol groups (e.g. eSH groups on cysteine residues, etc.), amine groups (e.g. eNH 2 groups on lysine residues) or carbohydrates. Cysteine, lysine or carbohydrate attachment sites can be added anywhere into a monoclonal antibody using site-directed mutagenesis, although the function of the monoclonal antibody must not be impaired [27] . For example, an antibody bound to a toxin can be targeted against a tumour. This can also be produced by genetic engineering where a DNA sequence coding for the specific toxin can be added to the end of the scFv chain region in the genome so they are transcribed at the same time [28] . Bispecific antibodies can target 2 separate epitopes with each arm of the Fab portion. They can be produced by chemical cross-linking of IgG, Fab or scFv fragments or through the generation of a 'hybrid hybridoma' [29] .