Monoclonal antibodies

Antibodies (IgA, IgD, IgE, IgG, IgM) are proteins made by B cells. When a pathogen enters, many different B cells respond, each making an antibody against a different part (epitope) of it. The mixture is polyclonal. That suits the body, but it is too mixed for laboratory use. A monoclonal antibody (MAb) binds just one epitope.

The difficulty: B cells are hard to grow in culture and die quickly. In 1975, Köhler and Milstein solved this. They fused antibody-making plasma cells with myeloma (cancer) cells, which divide forever, using PEG. The fused cells, hybridomas, combine the best of both: they grow indefinitely and keep making one kind of antibody.

To pick out the hybridomas, the cells are grown in HAT medium (hypoxanthine, aminopterin, thymidine). The specially engineered myeloma cells cannot survive in it; unfused B cells die naturally after a short time; only the hybridomas survive and multiply.

rDNA technology has improved them further. Monoclonal antibodies from mice can cause reactions in humans, so human parts are added, giving chimeric or humanised antibodies that work better in people.

Uses:

• Diagnostic kits, such as home pregnancy tests.
• Imaging cancer: labelled antibodies that bind only tumour cells show where a tumour is.
• Targeted therapy: antibodies carry toxins or drugs straight to cancer cells, sparing healthy ones.