23.02.2. Proteins that Function through Specific Targeting Activity

Although the use of antibodies as therapies for a variety of pathologies has been postulated for over one hundred years, a number problems associated with their use were observed. In particular, variability caused by their polyclonal nature and adverse immunological side effects had blunted their effectiveness as therapeutic agents. However, the development of monoclonal antibodies, in which a myeloma cell line that has lost its ability to secrete antibodies is fused with healthy antibody secreting B-cells, coupled with the ability to modify their immunogenicity by protein engineering or “humanising” them has revolutionised their use. The resultant immortalised fused cells (hybridomas) are able to continuously secrete industrial quantities of highly specific, single epitope antibodies for use in a number of diseases particularly cancer and autoimmune diseases. In 1986, Muromonab-CD3, used to combat tissue rejection in renal transplantation was the first monoclonal antibody approved by the FDA. To date, some 150 monoclonal antibodies are used to treat disease.