Bifunctional antibodies: concept, production and applications.

Immunoglobulins, or antibodies, are monospecific, bivalent antigen-binding molecules. Bifunctional antibodies are bispecific, with each arm binding to a different antigen, and may be produced by biological or chemical methods. Biological production involves the fusion of two monoclonal antibody-producing hybridomas or of an immunised spleen cell and a hybridoma. The resulting hybrid hybridomas (quadromas or triomas) secrete a mixture of parenteral monoclonal antibodies and bifunctional antibody. In chemical production, the parental monoclonal antibodies can be 'chopped up and reconstituted' to produce the bifunctional antibody only. Bifunctional antibodies have a variety of potential uses. They were originally proposed as an aid to cancer chemotherapy where one of the arms of the antibody would bind to a tumour marker and the other to a drug, toxin, or cytotoxic cell. Functional agents can thus be target directly onto tumour cells, accumulating with higher density, yet with reduced side effects for the patient. Further applications have been proposed involving enzyme immobilization and novel immunoassay techniques. This review describes developments that have taken place in bifunctional antibody technology to date.