Monoclonal Antibodies

Monoclonal antibodies are a specific, single type of antibody. The prefix 'mono-' means 'one', and the ending 'clonal' indicates that these antibodies are clones of each other; they are all the same. Scientists can clone B cells to produce monoclonal antibodies, where each antibody is produced from copies of the same cell.

How are monoclonal antibodies produced?

Monoclonal antibodies are produced 'naturally' in the body during the immune response, specifically the humoral response. Here, monoclonal antibodies are produced by one type of B cell (B lymphocyte), which synthesises the specific antibody that is complementary to the antigen of the pathogen being responded to. You can learn more about how and why B cells produce antibodies in our article on the humoral response.

Producing antibodies in a laboratory

Monoclonal antibodies can also be manufactured in laboratories for use in scientific research and medicine. In medical environments, they can be produced using hybridoma techniques.

In this process, a mouse is injected with an antigen for which a complementary antibody is being produced. This triggers a natural immune response in the mouse. The mouse's lymphocytes produce antibodies specific to the antigen.

Then, the spleen cells of the mouse, which synthesise the antibody-producing lymphocytes, are removed in a small operation.

These spleen cells are fused with human myeloma cells, which are cancerous white blood cells. The point of using cancerous cells is that they divide rapidly, and so many copies of this fused cell can be created in a short amount of time.

This fusion forms hybridoma cells that indefinitely divide to produce millions of antibodies. These antibodies are all identical to one another and specific to the original antigen.

Advantages and disadvantages

An advantage of this method is that scientists are able to produce large amounts of antibodies for use in research and medicine. Once a hybridoma cell has been produced, researchers can harvest virtually an endless amount of the antibodies required.

However, a clear disadvantage of this method is the ethical issues involved. Animals used in research cannot consent to the experiments being performed on them. Although steps are usually taken to reduce the pain they experience, lab animals may still experience pain during procedures such as surgeries.

What are monoclonal antibodies used for?

Monoclonal antibodies have significant value in science and medicine, where they can be used for testing for specific disease-causing antigens and for delivering targeted medication. Monoclonal antibodies are used to diagnose diseases such as HIV and conditions such as pregnancy.

Direct monoclonal antibody therapy

Monoclonal antibodies can be used to target specific cell types, such as cancer cells. Those that are complementary to the antigens on cancer cells can be given to patients. The attachment of monoclonal antibodies to the antigens on cancer cells blocks the chemical signals which stimulate their uncontrolled growth.

This prevents tumours from growing and spreading around the body, allowing for targeted chemotherapy to be more effective at destroying cancerous cells and preventing the progression of cancer. An example of this is the use of the Herceptin monoclonal antibody to treat breast cancer.

Direct monoclonal antibody therapy is currently one of the most successful cancer treatments. An advantage of this type of therapy is that it causes far fewer side effects than other types of monoclonal antibody therapy because the antibodies are non-toxic and highly specific.

Fig. 1 - Diagram of monoclonal antibodies attached to antigens on a cancer cell

Indirect monoclonal antibody therapy

Another method of treating cancer is the use of indirect monoclonal antibody therapy. This is when a radioactive or cytotoxic drug is attached to the monoclonal antibodies introduced into patients. When the antibody attaches to the antigens on cancer cells, it kills the cells.

Again, an advantage of this type of therapy is that it is highly specific, so only cancer cells are targeted. However, the use of toxic drugs may cause more side effects for patients. Another key advantage of both direct and indirect monoclonal antibody therapies is that they can be used in much smaller doses than other medications because they are specific. This saves money and reduces the chance of side effects.

Using monoclonal antibodies for medical diagnosis

Monoclonal antibodies are used in over a hundred different diagnostic products. This includes the ELISA test (Enzyme-linked immunosorbent assay), which has been developed to diagnose several diseases, including HIV and hepatitis B and C. Monoclonal antibodies are also used to diagnose diseases, such as influenza and chlamydia.

Monoclonal antibodies are important in helping to identify the presence of certain cancers, such as prostate cancer. Men with prostate cancer often produce a higher amount of a prostate-specific antigen (PSA). Doctors can use specific monoclonal antibodies to measure the amount of PSA in a person's blood. If this is unusually high, it may indicate the presence of cancer in the prostate, and give evidence for further diagnostic tests.

Monoclonal antibodies and pregnancy testing

Monoclonal antibodies are also used in pregnancy tests. When a pregnancy is diagnosed early, people can adjust their lifestyle accordingly to accommodate their growing child (eg by not drinking) or, if the pregnancy is unwanted, make plans to get an abortion before the fetus has developed past the point at which it is still legal. Therefore, having easy access to pregnancy tests is crucial. Monoclonal antibodies have made it possible to develop tests that can be taken at home and are relatively inexpensive.

These tests work by identifying the hormone human chorionic gonadotropin (hCG), which is produced by the placenta during pregnancy. This hormone can be found in the urine of pregnant people. If hCG is present, it will bind to the complementary antibodies on the testing strip of the pregnancy test. These antibodies are linked to coloured particles. The hCG-antibody-color complex then moves up along the testing strip until trapped by a second antibody, which produces a coloured line, indicating a positive test. This is broadly how lateral flow tests for COVID-19 operate, too.

Fig. 2 - How a positive pregnancy test occurs

Monoclonal antibodies and ethical usage

While the use of monoclonal antibodies is undoubtedly beneficial in diagnosing and treating certain conditions, there are also ethical issues associated with their development and usage.

As seen previously, monoclonal antibodies are most commonly produced using mice. In this process, mice are exposed to non-self material, including diseases. For instance, B cells in mice may be mixed with cancer cells to ensure their B cells duplicate quickly. While steps are taken to minimize the suffering of the animals involved, questions are raised as to how ethical it is to induce cancer and potentially other diseases in animals that cannot consent to their testing. It must also be asked if patients should be told if the monoclonal antibodies used for their treatment have come from genetically modified animals.

In some methods of production, monoclonal antibodies are produced from B cells donated by humans. With this method, is it right to keep donors anonymous, or should patients be able to find out where the B cells used in their treatment have come from?

In some cases, the monoclonal antibodies in disease treatment have been associated with severe side effects and even deaths.