What monoclonal antibodies are

1. An antibody binds only to the antigen whose shape is complementary to its binding sites, which makes antibodies extremely precise tools for finding one particular molecule.
2. The antibodies in your blood after an infection come from many different lymphocytes, so they are a mixture of slightly different shapes.
3. Monoclonal antibodies are different because they all come from a single clone of cells, so every antibody molecule is identical and binds to exactly the same antigen.
4. Scientists can choose the antigen, so monoclonal antibodies can be made to bind to a hormone, a protein on a pathogen, a chemical in the blood or a protein found only on cancer cells.
5. Making large amounts of one antibody is difficult, because a lymphocyte that makes the antibody does not divide when it is grown outside the body.
6. The solution is to join the lymphocyte to a cell that does divide, which is the basis of the method used to produce them.

Producing monoclonal antibodies

1. Monoclonal antibodies are produced in a series of steps.
   1. A mouse is injected with the chosen antigen, such as a protein found on a particular pathogen.
   2. The mouse's immune system responds, and its lymphocytes begin to produce antibodies complementary to that antigen.
   3. The lymphocytes are removed from the mouse, usually from its spleen.
   4. The lymphocytes are fused with tumour cells, which are cells that divide over and over without stopping.
   5. Each fused cell is called a hybridoma cell.
   6. The hybridoma cells are separated and tested, and a single hybridoma cell that makes the wanted antibody is selected.
   7. The selected cell is grown in a culture, where it divides repeatedly to produce a clone of identical hybridoma cells.
   8. The clone releases large amounts of one antibody, which is collected from the culture and purified.
2. The hybridoma combines the useful property of each parent cell.
   1. From the lymphocyte it inherits the ability to make one specific antibody.
   2. From the tumour cell it inherits the ability to divide rapidly and indefinitely.
3. Because all the cells in the culture come from one hybridoma cell, all the antibodies they release are identical, which is where the name monoclonal comes from.
4. The culture can be kept going for years, so a steady supply of the same antibody can be produced for tests and treatments.

Pregnancy tests

1. A developing embryo releases a hormone called human chorionic gonadotrophin, or hCG, which passes into the mother's blood and then into her urine.
2. A home pregnancy test uses monoclonal antibodies that are complementary to hCG to detect it in a urine sample.
3. The test stick has three important zones, each containing a different set of monoclonal antibodies.
   1. The reaction zone near the tip holds mobile antibodies that bind to hCG and that carry a coloured dye or a blue bead.
   2. The test line holds antibodies fixed to the strip that also bind to hCG.
   3. The control line holds fixed antibodies that bind to the mobile antibodies themselves, whether or not they are carrying hCG.
4. Urine is placed on the tip of the stick and soaks along the strip, carrying the mobile antibodies with it.
5. If hCG is present, it binds to the mobile antibodies, and the hCG-antibody complexes are then caught by the fixed antibodies at the test line, which turns coloured.
6. If there is no hCG, the mobile antibodies pass the test line without being caught, so the test line stays blank.
7. In both cases the remaining mobile antibodies are caught at the control line, which turns coloured to show that the test has worked.

Detecting disease

1. Monoclonal antibodies are used in hospital laboratories to detect and measure particular molecules in samples of blood.
2. Men with prostate cancer often have raised levels of a protein called prostate-specific antigen, or PSA, in their blood.
3. Monoclonal antibodies complementary to PSA are attached to a dye or a fluorescent marker and mixed with a blood sample.
4. The antibodies bind only to PSA, so the amount of colour or fluorescence shows how much PSA is present.
5. A high PSA level is a signal that the man should have further tests, although PSA can also be raised by other conditions of the prostate.
6. Monoclonal antibodies are also used to locate diseased tissue inside the body.
   1. Antibodies that bind to an antigen found only on cancer cells are attached to a radioactive or fluorescent marker.
   2. The labelled antibodies are injected and travel in the blood until they bind to the cancer cells.
   3. A scanner detects where the marker has built up, which shows the position and size of a tumour.
7. The same approach can detect a pathogen in a blood or tissue sample, or find the position of a blood clot, by choosing an antibody that binds to that pathogen or to a protein in the clot.

Treating disease

1. Monoclonal antibodies can potentially be used to treat cancer by carrying a treatment directly to the cancer cells.
2. A monoclonal antibody that binds to an antigen found only on the surface of cancer cells is made first.
3. A drug, a toxin or a radioactive substance is then attached to the antibody.
4. When the antibody is injected, it binds only to the cancer cells, so the attached substance kills the cancer cells while leaving healthy cells largely unharmed.
5. Some monoclonal antibodies work without any attached substance, by binding to cancer cells and marking them so that the patient's own white blood cells destroy them.
6. Targeting the treatment in this way should cause fewer side effects than treatments such as chemotherapy, which damage healthy dividing cells throughout the body.
7. Monoclonal antibodies also have disadvantages that have limited their use.
   1. They have caused more side effects than was expected when they were first developed, such as fever, vomiting and a fall in blood pressure.
   2. They are expensive to develop and to produce.
   3. Their production uses mice, which some people object to on ethical grounds.