Monoclonal Antibodies

A mouse is injected with the chosen antigen. The mouse's lymphocytes produce antibody against this antigen. These antibody-producing lymphocytes are removed from the mouse's spleen and fused with tumour (myeloma) cells. The fused cell is called a hybridoma — it makes the specific antibody (from the lymphocyte) AND can divide indefinitely (from the tumour cell). The hybridoma is cloned in culture so many identical cells are produced. The monoclonal antibodies released into the culture medium are then collected, purified and used.

Normal lymphocytes can only divide a limited number of times, so they cannot be kept in culture long enough to produce large quantities of antibody. Tumour cells divide rapidly and indefinitely but don't make the specific antibody we want. Fusing the two produces a hybridoma that combines both properties — it makes the specific antibody AND keeps dividing — so large amounts of the antibody can be produced.

All the antibodies in the batch are produced by a single clone of identical hybridoma cells. Because the cells are genetically identical, they all make antibodies with exactly the same binding site, which fits only one antigen.

Mice are killed to remove their spleens for the lymphocytes, which raises animal welfare concerns. UK law requires a Home Office licence under the Animals (Scientific Procedures) Act 1986 and proof that the work cannot be done without animals. The resulting antibodies are partly mouse protein, which can trigger an immune reaction in human patients (this is now reduced by humanising the antibody). On balance, the medical benefits (e.g. cancer drugs that save UK patients' lives) currently justify the carefully regulated use of mice.

Pregnant women's urine contains the hormone hCG, released by the placenta. The test stick contains mobile monoclonal antibodies attached to coloured beads — these antibodies are specific to hCG. If hCG is present in the urine, it binds to the mobile antibodies and the complex flows along the strip to a fixed test line. The fixed line contains a second set of anti-hCG monoclonal antibodies which trap the complex, building up enough coloured beads to make a visible line — a positive result.

(1) Detecting the hormone hCG in pregnancy tests. (2) Diagnosis of diseases in laboratories, by detecting specific molecules in blood or tissue (e.g. cancer markers). (3) Research — labelled with a fluorescent dye to locate specific molecules in a cell or tissue under a microscope. (4) Treating diseases such as cancer, by delivering drugs, radiation or toxins directly to cancer cells.

A monoclonal antibody is chosen that binds only to an antigen on the surface of cancer cells (e.g. HER2 on some breast cancers). A drug, radioactive isotope or toxin is attached to the antibody. When injected into the patient, the antibody binds only to the cancer cells because of its specificity, delivering the payload directly to them. Healthy cells lack the target antigen so they are not affected, reducing the side effects compared with traditional chemotherapy.

Monoclonal antibodies are highly specific — they bind only their target molecule, so they often damage healthy tissue less than traditional chemotherapy. They have produced effective NHS treatments such as Herceptin for HER2-positive breast cancer. However, side effects are still common (allergic reactions, low blood pressure, flu-like symptoms), the original mouse-derived antibodies could trigger an immune response in patients, and manufacture is very expensive — single courses can cost the NHS tens of thousands of pounds per patient, so NICE has to decide whether each drug is cost-effective. Treatments also only work for patients whose cancer expresses the target antigen. On balance, monoclonal antibodies have been a valuable addition to NHS medicine but have not become the universal 'magic bullet' scientists originally hoped.