Monoclonal Antibodies to Treat Cancer
One way the immune system attacks foreign substances in the body is by making large numbers of antibodies. An antibody is a protein that sticks to a specific protein called an antigen. Antibodies circulate throughout the body until they find and attach to the antigen. Once attached, they can recruit other parts of the immune system to destroy the cells containing the antigen.
Researchers can design antibodies that specifically target a certain antigen, such as one found on cancer cells. They can then make many copies of that antibody in the lab. These are known as monoclonal antibodies (mAbs).
Monoclonal antibodies are used to treat many diseases, including some types of cancer. To make a monoclonal antibody, researchers first have to identify the right antigen to attack. For cancer, this is not always easy, and so far mAbs have proven to be more useful against some cancers than others.
Over the past couple of decades, the US Food and Drug Administration (FDA) has approved more than a dozen mAbs to treat certain cancers. As researchers have found more antigens linked to cancer, they have been able to make mAbs against more and more cancers. Clinical trials of newer mAbs are now being done on many types of cancer.
Types of monoclonal antibodies
Different types of monoclonal antibodies are used in cancer treatment.
Naked monoclonal antibodies
Naked mAbs are antibodies that work by themselves. There is no drug or radioactive material attached to them. These are the most common type of mAbs used to treat cancer.
Most naked mAbs attach to antigens on cancer cells, but some work by binding to antigens on other, non-cancerous cells, or even free-floating proteins.
Naked mAbs can work in different ways.
- Some boost a person's immune response against cancer cells by attaching to them and acting as a marker for the body's immune system to destroy them. An example is alemtuzumab (Campath®), which is used to treat some patients with chronic lymphocytic leukemia (CLL). Alemtuzumab binds to the CD52 antigen, which is found on cells called lymphocytes (which include the leukemia cells). Once attached, the antibody attracts immune cells to destroy these cells.
- Some naked mAbs boost the immune response by targeting immune system checkpoints. (See Immune checkpoint inhibitors to treat cancer.)
- Other naked mAbs work mainly by attaching to and blocking antigens on cancer cells (or other nearby cells) that help cancer cells grow or spread. For example, trastuzumab (Herceptin®) is an antibody against the HER2 protein. Breast and stomach cancer cells sometimes have large amounts of this protein on their surface. When HER2 is activated, it helps these cells grow. Trastuzumab binds to these proteins and stops them from becoming active.
Conjugated monoclonal antibodies
Monoclonal antibodies (mAbs) joined to a chemotherapy drug or to a radioactive particle are called conjugated monoclonal antibodies. The mAb is used as a homing device to take one of these substances directly to the cancer cells. The mAb circulates throughout the body until it can find and hook onto 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.
Conjugated mAbs are also sometimes referred to as tagged, labeled, or loaded antibodies.
Radiolabeled antibodies: Radiolabeled antibodies have small radioactive particles attached to them. Ibritumomab tiuxetan (Zevalin®) is an example of a radiolabeled mAb. This is an antibody against the CD20 antigen, which is found on lymphocytes called B cells. The antibody delivers radioactivity directly to cancerous B cells and can be used to treat some types of non-Hodgkin lymphoma.
Treatment with this type of antibody is sometimes known as radioimmunotherapy (RIT).
Chemolabeled antibodies: These mAbs have powerful chemotherapy (or other) drugs attached to them. They are also known as antibody-drug conjugates (ADCs). (The drug is often too powerful to be used on its own - it would cause too many side effects if not attached to an antibody.)
Chemolabeled antibodies used to treat cancer include:
- Brentuximab vedotin (Adcetris®), an antibody that targets the CD30 antigen (found on lymphocytes), attached to a chemo drug called MMAE. This drug is used to treat Hodgkin lymphoma and anaplastic large cell lymphoma.
- Ado-trastuzumab emtansine (Kadcyla®, also called TDM-1), an antibody that targets the HER2 protein, attached to a chemo drug called DM1. It's used to treat some breast cancer patients whose cancer cells have too much HER2.
A related drug known as denileukin diftitox (Ontak®) is an immune system protein known as interleukin-2 (IL-2) attached to a toxin from the germ that causes diphtheria. Although it's not an antibody, IL-2 normally attaches to certain cells in the body that contain the CD25 antigen, which makes it useful for delivering the toxin to these cells. Denileukin diftitox is used to treat lymphoma of the skin (also known as cutaneous T-cell lymphoma). It's also being studied for use against a number of other cancers.
Bispecific monoclonal antibodies
These drugs are made up of parts of 2 different mAbs, meaning they can attach to 2 different proteins at the same time. An example is blinatumomab (Blincyto), which is used to treat some types of acute lymphocytic leukemia (ALL). One part of blinatumomab attaches to the CD19 protein, which is found on some leukemia and lymphoma cells. Another part attaches to CD3, a protein found on immune cells called T cells. By binding to both of these proteins, this drug brings the cancer cells and immune cells together, which is thought to cause the immune system to attack the cancer cells.
Possible side effects of monoclonal antibodies
Monoclonal antibodies are given intravenously (injected into a vein). The antibodies themselves are proteins, so giving them can sometimes cause something like an allergic reaction. This is more common while the drug is first being given. Possible side effects can include:
- Low blood pressure
Compared with chemotherapy drugs, naked mAbs tend to have fewer serious side effects. But they can still cause problems in some people. Some mAbs can have side effects that are related to the antigens they target. For example:
- Bevacizumab (Avastin®) is an mAb that targets a protein called VEGF that affects tumor blood vessel growth. It can cause side effects such as high blood pressure, bleeding, poor wound healing, blood clots, and kidney damage.
- Cetuximab (Erbitux®) is an antibody that targets a cell protein called EGFR, which is found on normal skin cells (as well as some types of cancer cells). This drug can cause serious rashes in some people.
Conjugated antibodies can be more powerful than naked mAbs, but they can also cause more side effects. The side effects depend on which type of substance they're attached to.