Monoclonal Antibodies and Their Side Effects

One way the body's immune system attacks 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 force 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 referred to as targeted therapy because they have a specific target on a cancer cell that they aim to find, attach to, and attack. But other monoclonal antibodies act like immunotherapy because they make the immune system respond better to allow the body to 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.

These are made from mouse proteins and the names of the treatments end in -omab. C himeric: These proteins are a combination of part mouse and part human and the names of the treatments end in -ximab.

These proteins are a combination of part mouse and part human and the names of the treatments end in -ximab. H umanized: These are made from small parts of mouse proteins attached to human proteins and the names of the treatments end in -zumab

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 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.

), 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 and Their Side Effects.)

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

Conjugated mAbs are combined with 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. 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 cancer cells. It is made of both an mAb drug (rituximab) and a radioactive substance (Yttrium-90). 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, then the radiation affects the target and nearby cells to a certain extent.

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 cancer cells. It is made of both an mAb drug (rituximab) and a radioactive substance (Yttrium-90). 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, then the radiation affects the target and nearby cells to a certain extent. Chemolabeled antibodies: These mAbs have powerful chemotherapy (or other) drugs attached to them. Examples include: Brentuximab vedotin (Adcetris), 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 antibody that targets the HER2 protein, attached to a chemo drug called DM1.

These mAbs have powerful chemotherapy (or other) drugs attached to them. Examples include:

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 leukemia. 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:

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: