Monoclonal Antibody
Cripto-1 Monoclonal Antibody
Monoclonal antibodies (MAbs) are a type of molecule produced by the immune system that are all identical and that can be produced in large quantities from a single original B cell. They may be used for treating cancer because they circulate in the body and bind both selectively and with high affinity to specific antigens (a type of protein) on the surface of tumours, in the case of cancer, and help to kill them. The MAbs can act by helping other effector molecules of the immune system to "punch holes" in the tumour cell. Alternatively MAbs may be used as a vehicle for delivering drugs or radioactive agents to any cells in the body that display the antigen recognised by the MAbs. A third way in which antibodies can cause cancer cells to die is by interfering with their cell signalling or regulation pathways. All cells need to receive "signals" from their environment in order to grow and interact with other cells. When antibodies bind to an antigen on the cell surface, these signals can either be blocked causing the cells to die or actually signal the tumour to undergo cell death.
Many MAbs that have been used in the past were made in animals such as mice. Unfortunately when these were used in patients, the benefits were short lived because the patient's immune system ultimately recognized the MAb as foreign and cleared it from the body before it could work. With the advent of genetic engineering technology, two new ways to generate MAbs have developed. The first method takes the important parts of the mouse antibody and cut and pastes it onto human-looking antibodies. The second method has been to genetically engineer mice with human genes so that they can produce a human antibody when immunised with antigens. The result of these methods is a human antibody that is better tolerated by patients for treatment and that can be produced on a large scale.
Under the Prima BioMed Biological Therapy program, a fully human antibody is being produced. The antigen that these MAbs are recognising is Cripto-1, a protein found in high levels on the surface of many tumours. The high expression levels of Cripto-1 on tumours compared with normal tissues makes it an attractive target. Past investigations have demonstrated that binding of Cripto-1 by rat antibodies has induced cells to die by a process known as apoptosis. Injection of these antibodies into mice has been able to both prevent tumour challenge and eradicate existing tumours. Current studies are examining whether the human versions of the rat antibodies can cause cancer cells to die in a similar manner.
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