3.9 - Monoclonal Antibodies

Producing monoclonal antibodies

• Antibodies are proteins made by a type of white blood cell called a B-lymphocyte.
• Each B-lymphocyte makes just one kind of antibody, which binds to one particular antigen.
• Monoclonal antibodies are antibodies produced from many clones of a single B-lymphocyte - so they are all identical and all bind to the same specific protein antigen.

How they're made

1. A mouse is injected with the antigen the antibody is wanted against, so its immune system produces B-lymphocytes that make exactly that antibody.
2. These B-lymphocytes are taken from the mouse. On their own they're no use for mass production, because lymphocytes don't divide easily.
3. Each B-lymphocyte is fused with a fast-dividing tumour cell (also called a myeloma cell). Tumour cells don't make antibodies, but they divide rapidly.
4. The fused cell - a hybridoma - does both: it makes the antibody like the lymphocyte, and divides quickly like the tumour cell.
5. A single hybridoma is cloned to give many identical hybridoma cells, all dividing and all making the same antibody.
6. The antibodies produced are collected and purified, giving a large amount of one specific antibody.

Why they're so useful

• Because the starting antigen can be chosen freely, a monoclonal antibody can be made to bind to almost anything.
• For example, it can target an antigen found only on the surface of one type of cell - which is what makes them so useful for targeting a particular cell or chemical in the body.

Monoclonal antibodies in diagnosis

• A monoclonal antibody binds to one specific target, which makes it useful in several kinds of diagnosis.
• Three uses: measuring a chemical, detecting a pathogen, and showing where particular cells are inside the body.

Measuring the level of a chemical

• Because a monoclonal antibody binds only one specific chemical, it can measure how much of that chemical is in a sample.
• An antibody that binds only to a particular hormone (or other chemical) is added to a blood sample.
• The amount that binds reflects how much of the chemical is in the blood - so it gives a measure of its level.
• This lets doctors check, for example, the concentration of a hormone in a patient's blood.

Detecting a pathogen

• A monoclonal antibody can be made to bind the antigens on a particular pathogen, to test whether that pathogen is present in a sample.
• If the pathogen is there, its antigens bind the antibody and the test gives a positive result.
• If it isn't there, nothing binds.
• This is how monoclonal antibodies are used in diagnostic tests for particular infections.

Locating cells in the body

• To show where a particular cell is, the antibody is labelled with a fluorescent dye or a radioactive substance. Wherever it binds, the label can be detected, so the position of its target shows up.
• This is how cancer can be located:
  1. Antibodies are made to bind tumour markers - antigens found on cancer cells but not on normal cells.
  2. The labelled antibodies are given through a drip.
  3. A camera that picks up the label shows a bright spot wherever there are cancer cells.
• Doctors can then see where the cancer is, how big it is, and whether it's spreading.

Monoclonal antibodies in treatment

• Monoclonal antibodies can be used to treat cancer, using their ability to bind only to tumour markers on cancer cells.
• An anti-cancer drug is attached to the antibodies. This drug can be:
  • A radioactive substance
  • A toxic drug
  • A chemical that stops cells growing and dividing
• The antibodies are given to the patient through a drip, travel in the blood and bind only to the cancer cells, delivering the drug straight to the tumour.
• This kills the cancer cells without harming the normal body cells nearby.
• In some cases the antibodies simply tag the cancer cells, so the patient's own white blood cells recognise them as foreign and destroy them.

Advantages and disadvantages

• Main advantage - targeting - The antibody binds only to its specific target, so treatment reaches the cancer cells while affecting fewer healthy cells. Ordinary treatments such as chemotherapy and radiotherapy damage normal body cells as well as cancer cells.
• Main drawback - side effects - Monoclonal antibodies cause more side effects than first expected, including fever, vomiting and low blood pressure, so they haven't become as widely used as scientists originally hoped.