What are Humanized Monoclonal Antibodies?
Monoclonal antibody therapy uses antibodies that are made in the lab rather than by a person’s own immune system. Once the antibodies are given, they may recruit other parts of the immune system to destroy the targeted antigen, such as a cancer cell.
The first monoclonal antibodies were typically made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they’re from a different species) and will mount a response against them. In the short term, this can sometimes cause an immune response. In the long term, it means that the antibodies may only work the first time they are given; after that, the body’s immune system is primed to destroy them before they can provide treatment.
Over time, researchers learned how to replace some parts of these mouse antibody proteins with human components. Antibodies with a mixture of mouse and human components are known as chimeric antibodies. As more human components were used in the mouse antibody, they were referred to as humanized antibodies. Some monoclonal antibodies are now fully human, which means they are likely to be even safer and may be more effective than earlier monoclonal antibodies. An even newer approach uses fragments of antibodies instead of whole ones. Smaller pieces may be better able to reach a tumor, which may make them more effective.
Clinical trials of monoclonal antibody therapy are being done on almost every type of cancer. As researchers have found more antigens that are linked to cancer, they have been able to make monoclonal antibodies against an array of cancers.
Two types of monoclonal antibodies are used in cancer treatments:
- Naked monoclonal antibodies are those without any drug or radioactive material attached to them.
- Conjugated monoclonal antibodies are those joined to a chemotherapy drug, radioactive particle, or cancer cell killing agent.
Naked monoclonal antibodies are the most commonly used monoclonal antibodies at this time. Although they all work by attaching themselves to specific antigens, they can be helpful in different ways. Some naked monoclonal antibodies attach to cancer cells to act as a marker for the body’s immune system to destroy them. An example of this is Campath® (alemtuzumab) which is used to treat some patients with B-cell chronic lymphocytic leukemia and is an antibody against the CD52 antigen, which is found on both B cells and T cells.
Some naked monoclonal antibodies don’t interact with a person’s immune system. Their effects come from their ability to attach to the specific antigens that are working parts of cancer cells or other cells that help cancer cells grow, and stop them from working. These monoclonal antibodies are also referred to as targeted therapies. Examples of FDA-approved monoclonal antibodies of this type include:
- Herceptin® (trastuzumab): Trastuzumab is an antibody against the HER2 protein. A large amount of this protein is present on tumor cells in some cancers. When HER2 is activated, it helps these cells grow. Trastuzumab stops these proteins from becoming active. It is used to treat breast cancers that have large amounts of the HER2 protein.
- Avastin® (bevacizumab): Bevacizumab targets the VEGF protein, which is made by tumor cells to develop new blood vessels to feed their growth. Bevacizumab attaches to VEGF, which blocks it from signaling for new blood vessels to form. This monoclonal antibody is used along with chemotherapy to treat some colorectal, lung, and breast cancers, and is being studied for use against other cancers.
Conjugated monoclonal antibodies are monoclonal antibodies that are attached to drugs, cancer killing agents, or radioactive substances. The monoclonal antibodies are used as homing devices to take these substances directly to the cancer cells. The monoclonal antibody circulates in the body until it can find and bind to the target antigen. It then delivers the toxic substance where it is needed most. This lessens the damage to normal cells in other parts of the body caused by the drug, cancer killing agent or radioactive substance.
The only conjugated antibody approved for treating cancer is Mylotarg® or gemtuzumab ozogamicin. It has a cancer killing agent called calicheamicin, attached to an antibody against the CD33 antigen, which is present on most leukemia cells. Mylotarg is used to treat some people with acute myelogenous leukemia. Clinical trials of other conjugates are also being done in people with certain leukemias, lymphomas, brain tumors, and breast cancer.