8.12 - 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 antigen, which makes it useful in several kinds of diagnosis and monitoring.

Testing for a pathogen

• An antibody can be made to bind the antigens on a particular pathogen, so it can test whether that pathogen is present in a sample.
• If the pathogen is there, its antigens bind the antibody and the test reads positive; if not, nothing binds.
• This is how diagnostic tests for particular infections work - for example, tests for Chlamydia or HIV.

Tissue typing before a transplant

• Different people have different antigens on their cell surfaces.
• A transplant is more likely to succeed if the donor's tissue antigens closely match the recipient's.
• Antibodies that bind particular antigens are used to check which antigens are present in the donor's and recipient's blood, so the two can be matched before the transplant goes ahead.

Monitoring the spread of malaria

• Antibodies can be made to bind the antigens of the malaria parasite.
• These detect the parasite in blood samples, so they can be used to find where malaria is occurring and track how an outbreak is 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.