Monoclonal Antibodies and Their Side Effects
One way the immune system protects the body from germs and other foreign substances 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 help 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 or Moabs).
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. Finding the right antigens for cancer cells is not always easy, and so far mAbs have proven to be more useful against some cancers than others.
NOTE: Some monoclonal antibodies used to treat cancer are sometimes considered to be a type of targeted therapy because they work by attaching to a specific target on a cancer cell and stopping it from functioning. But other monoclonal antibodies act like immunotherapy because they help the immune system find and attack cancer cells more effectively.
What mAbs are made of
Monoclonal antibodies are man-made proteins that act like human antibodies in the immune system. There are 4 different ways they can be made and are named based on what they are made of.
- Murine: These are made from mouse proteins, and the names of the treatments end in -omab.
- Chimeric: These proteins are a combination of part mouse and part human, and the names of the treatments end in -ximab.
- Humanized: These are made from small parts of mouse proteins attached to human proteins, and the names of the treatments end in -zumab
- Human: These are fully human proteins, and the names of the treatments end in -umab.
Types of mAbs used to treat cancer
Naked monoclonal antibodies
Naked mAbs are antibodies that have no drug or radioactive material attached to them. They work by themselves. 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 rituximab (Rituxan), which is used to treat some types of non-Hodgkin lymphoma (NHL) and other cancers. Rituxi20mab binds to the CD antigen, which is found on cells called B lymphocytes (which include some types of lymphoma 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 and Their Side Effects.)
- Other naked mAbs work mainly by attaching to and blocking proteins 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, which helps these cells grow. Trastuzumab binds to these proteins and stops them from becoming active.
Conjugated monoclonal antibodies
Conjugated mAbs are connected to a chemotherapy drug or a radioactive particle. These mAbs are 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. Conjugated mAbs are also sometimes referred to as tagged, labeled, or loaded antibodies.
Antibody-drug conjugates (ADCs): These mAbs have powerful chemotherapy (or other) drugs attached to them. Examples include:
- Brentuximab vedotin (Adcetris), an ADC made up of an antibody that targets the CD30 antigen (found on lymphocytes), attached to a chemo drug called MMAE
- Ado-trastuzumab emtansine (Kadcyla, also called TDM-1), an ADC made up of an antibody that targets the HER2 protein, attached to a chemo drug called DM1
Radiolabeled antibodies: Radiolabeled antibodies have small radioactive particles attached to them. The antibody delivers radioactivity directly to cancer cells. Treatment with this type of antibody is sometimes known as radioimmunotherapy (RIT). The drug and radiation are delivered directly to the target cells because the mAb looks for the target, and then the radiation affects the target and nearby cells to a certain extent.
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.
Bispecific T-cell engagers (BiTEs): In these drugs, one part attaches to a protein on cancer cells, and the other sticks to a protein on immune cells called T cells. This brings the immune cells into contact with the cancer cells, which helps the immune system mount a more effective response against them. BiTEs are becoming an important part of treatment for some types of cancer.
Possible side effects of monoclonal antibodies
Monoclonal antibodies are given intravenously (injected into a vein). The antibodies themselves are proteins, and giving them can sometimes cause an infusion reaction, which is something like an allergic reaction. This is more common while the drug is first being given. Possible symptoms can include:
- Fever
- Chills
- Weakness
- Headache
- Nausea
- Vomiting
- Diarrhea
- Low blood pressure
- Rashes
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.
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- References
The American Cancer Society medical and editorial content team
Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.
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Last Revised: December 20, 2023
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