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Monoclonal antibodies (MOABs), also known as MoAbs or mAbs, are artificial antibodies that are manufactured to target specific foreign substances (antigens) on the surface of cancer cells. Researchers are evaluating the effectiveness of these drugs as a form of biological therapy (also called immunotherapy) used to treat various cancers.
Antibodies are proteins produced by B lymphocytes (a type of white blood cell) or plasma cells to fight infections. Each B lymphocyte produces an antibody that recognizes a specific antigen. When the antibody makes contact with the antigen, it binds to it. This marks the antigen for destruction by cells of the immune system.
Each antibody is made up of two parts:
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Variable part. Recognizes the antigen, or exact structure of the foreign invader.
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Constant part. Also known as the tail, it is recognized by effector cells (immune system cells that perform a specific function in response to a stimulus) of the immune system, such as monocytes, macrophages, neutrophils and LAK cells. The constant part attracts working immune cells, which attack the structure to which the antibody is attached.
MOABs are considered to be a form of passive immunotherapy because they are made in a laboratory. To create monoclonal antibodies, scientists first inject human cancer cells into mice. When the mice make antibodies to the cells, the mouse cells that produce the antibodies are removed and fused with laboratory-grown cells. These hybrid cells, or hybridomas, produce abundant quantities of antibodies. The origin of the antibodies as a cloe of a single hybridoma cell provides the name monoclonal antibodies.
These hybrid cells are then injected into the human body where they attach to a predetermined area, usually the surface of certain cancer cells. When this occurs, the body recognizes the cancer cells as foreign and triggers the immune system to detect and attack the cells.
MOABs work in various ways. For instance, some MOABs attach to and block signals from the cancer cell that tell the tumor to grow faster. MOABs may also be used to treat cancer in the following ways:
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Bind to radioactive substances, anticancer drugs and toxins, delivering poison to a tumor and helping to destroy it while ensuring that healthy cells remain unaffected (conjugated antibodies).
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Enhance a patient’s immune response to a specific cancer.
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Interfere with the growth of cancer cells.
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Block the growth of blood vessels that supply tumors (antiangiogenesis).
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Carry radioisotopes that may help diagnose certain cancers, including those of the colon and rectum, ovaries and prostate.
However, monoclonal antibodies have certain limitations. For example, they can travel only a few cell layers from where blood vessels enter a tumor. As a result, they do not kill cancer cells that are distant from a blood vessel. In addition, monoclonal antibodies linked to anticancer medications do not always carry enough of the medication to be effective. For example, antibodies combined with radioactive substances may be effective in treating lymphomas, but not in treating cancers that are less sensitive to radiation, such as those of the colon, pancreas, stomach and esophagus.
Clinical research continues on methods to improve the cancer-fighting effectiveness of MOABs. For example, there is some evidence that while mouse hybridoma cells work well in humans initially, the body eventually begins to recognize them as foreign and starts destroying them as they enter the body.
As a result, researchers have begun combining the part of the mouse antibody responsible for recognizing specific tumor antigens with other parts from a human antibody gene. This combination antibody is known as a “chimeric” or “humanized” monoclonal antibody. Because it appears similar to a normal human antibody, there is a better chance it will not be destroyed by the patient’s immune system.
Monoclonal antibodies have also been developed to treat other conditions, including asthma and multiple sclerosis. Some MOABs used for cancer treatment are used to treat conditions such as rheumatoid arthritis and systemic lupus erythematosus.
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