What are Antibodies? What are Monoclonal Antibodies? The Science - How are Monoclonal Antibodies Made? Role of Biotechnology Mechanism and Use of Monoclonal Antibodies Bibliography

Antibodies are one of the existing mechanisms of the body that are being used to treat and diagnose disease. Monoclonal antibodies are just like antibodies except they are artificially produced from the clones of a single cell.

What are Antibodies?

Antibodies are proteins that attach to foreign material in the body (such as bacteria and viruses) and are released by certain cells of the immune system. They "mark" these foreign material for removal or destruction by other components of the immune system.

Any foreign substance that can make the immune system release antibodies is called an antigen. For example, a flu virus is an antigen because it makes the immune system release antibodies.

Antibodies are unique because they are made in response to specific antigens. In fact, antigens and antibodies fit like puzzle pieces. For example, a particular type of flu virus prompts the immune system to produce antibodies that fit that particular type of flu virus.

What are Monoclonal Antibodies?

In the lab, monoclonal antibodies are produced from the clones of one cell. That's why they are called "monoclonal." This basically means that every monoclonal antibody produced by this cell is exactly the same. This gives them the collective specificity that can be used in treatment and diagnosis.

The Science - How are Monoclonal Antibodies Made?

Monoclonal antibodies are made by multiple, identical copies (i.e. clones) of a cell called a hybridoma.

Hybridoma cells are created by the fusion of two cells in order to combine the distinct characteristics of the two cells into one cell. One of these cells is an antibody producing cell (B-Lymphocyte) from a lab mouse and the other is a tumour cell called a myeloma. The tumour cells can donate to a normal cell the ability to grow indefinitely and at a rate that exceeds normal cell growth. This means that when hybridoma cells are grown in the lab, they replicate faster than normal antibody producing cells in the body, and the individual hybridomas produce the specific antibodies for an indefinite time period.

A hybridoma will produce the monoclonal antibody that was originally produced by the B-Lymphocyte cell. The kind of antibody the original B-Lymphocyte cell produces depends on the kind of antigen that was injected into the mouse before the B-Lymphocyte cells were harvested. For example, if the mouse was injected with a flu virus, the mouse will have B-Lymphocytes that produce flu antibodies. When fused with a tumour cell to make a hybridoma, the hybridoma will produce monoclonal antibodies against the flu.

After the hybridoma cells are created and chosen for effectiveness in the lab, they are put into media that can help them grow and subsequently produce the monoclonal antibodies. There are two ways of doing this. One is to grow them in a flask in a lab (In Vitro), and the other is to grow them in the stomach lining of mice. Injecting the hybridomas into the mice is a more familiar method of harvesting monoclonal antibodies.

To learn about other uses of mice, go to Genetically Engineered Mice.

Role of Biotechnology

Biotechnology has been essential for the creation of monoclonal antibodies. Two key biotechnology techniques, cell fusion and cell culture, have been used extensively in the production of monoclonal antibodies.

Monoclonal antibodies are created with cell fusion technology (the creation of hybridomas) and cell culture technology (growing myelomas and hybridomas in the lab).

Scientists have been able to make monoclonal antibodies in the lab since 1975. Initially, there was much excitement surrounding their discovery. But because they could only be made with mouse cells, their use was limited in humans and often unsuccessful. For a long time, this was the biggest problem with monoclonal antibodies.

When injected into patients, the monoclonal antibodies triggered an immune system response since the human body recognized them as foreign. Repeated injections resulted in rapid clearance of the mouse antibody, which made it ineffective. In some cases, second or subsequent injections led to a life-threatening hypersensitivity reaction. Genetic engineering is being used to overcome this serious obstacle.

Genetic engineering techniques allow scientists to make "humanized" (almost human) monoclonal antibodies by grafting a human antibody onto a mouse one. Only the portion of the mouse antibody that is critical in binding to a target antigen stays unchanged. Humanized monoclonal antibodies are approximately 90 percent human. This makes them less likely to be rejected by the human body, and more likely to be effective.

Humanized monoclonal antibodies are the basis of the drugs Herceptin®, which is used to treat breast cancer and Zenapax®, which is used in the prevention of kidney transplant rejection.

Research is now underway to produce fully human antibodies from transgenic mice.

Mechanism and Use of Monoclonal Antibodies

The basic mechanism of a monoclonal antibody is the same as an antibody produced by the body. However, when monoclonal antibodies are used in the diagnosis and treatment of diseases, certain substances are often added to them to give them their therapeutic and diagnostic characteristics. They can also be used on their own to block or encourage certain responses from the immune system.

When monoclonal antibodies are used in therapy, they are often attached to different drugs or toxins, which are then delivered to the target cells without harming the other cells in the body. Used alone, they can encourage the body's own immune system to recognize certain cells as foreign and launch an attack. In diagnosis, radioactive markers are attached to them to locate a certain kind of cell within the body. They are used in diagnostic imaging of internal organs and tumours.

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