CAR T-Cell Therapies

Chimeric antigen receptor (CAR) T-cell therapy

Your immune system helps keep track of all the substances normally found in your body. Any new substance the immune system doesn't recognize raises an alarm, causing the immune system to attack it. CAR T-cell therapy is a promising new way to get immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells. CAR T-cell therapies are sometimes talked about as a type of gene or cell therapy, or an adoptive cell transfer therapy.

Cancer and the Immune System

To better understand how CAR T-cell therapies work, it can help to know a little more about the immune system and cancer. Your immune system has many different kinds of cells that work together to destroy foreign substances. First, the immune system has to recognize that these substances do not belong in the body. It does this by finding proteins on the surface of those cells, called antigens. Some immune cells, like T-cells, have their own proteins (called receptors) that attach to foreign antigens and help trigger other parts of the immune system to destroy the foreign substance. The relationship between antigens and immune receptors is like a lock and key. Just as every lock can only be opened with the right key, each foreign antigen has a unique immune receptor that is able to bind to it. Cancer cells also have antigens, but the immune system has a tougher time knowing cancer cells are foreign. If your immune cells do not have the right receptor (protein) to find a cancer cell's antigen, they cannot attach to it and help destroy the cancer cell.

The T-cells used in CAR T-cell therapies get changed in the lab to spot specific cancer cells by adding a man-made receptor (called a chimeric antigen receptor or CAR). This helps them better identify specific cancer cell antigens. Since different cancers have different antigens, each CAR is made for a specific cancer's antigen. For example, certain kinds of leukemia or lymphoma will have an antigen on the outside of the cancer cells called CD19. The CAR T-cell therapies to treat those cancers are made to connect to the CD-19 antigen and will not work for a cancer that does not have the CD19 antigen. The patient's own T-cells are used to make the CAR T-cells.

CAR T-cell Therapy Steps

The process for CAR T cell therapy can take a few weeks. First, T cells are removed from the patient’s blood using a procedure called leukapheresis. During this procedure, patients usually lie in bed or sit in a reclining chair. Two IV lines are needed because blood is removed through one IV, and then is returned to the body through the other. Sometimes a special type of IV line is used called a central venous catheter, that has both IV lines built in. The patient needs to remain still for 2 to 3 hours during the procedure. During leukopheresis, sometimes calcium levels can drop and cause numbness and tingling or muscle spasms. This can be easily treated with calcium, which may be given by mouth or through an IV .

After the white cells are removed from the patient, the T-cells are separated, sent to the lab, and genetically altered by adding the specific chimeric antigen receptor (CAR). This makes them CAR T-cells. It can take a few weeks to finish making CAR T-cells because a very large number of CAR T-cells are needed for this therapy. Once there are enough CAR T-cells, they will be given back to the patient to launch a precise attack against the cancer cells.

A few days before a CAR T-cell infusion, a patient might receive chemotherapy to help lower the number of other immune cells so the CAR T-cells have a better chance to get activated to fight the cancer.  This chemotherapy is usually not very strong because CAR T-cells work best when there are some cancer cells to attack. Once the CAR T-cells start binding with cancer cells, they start to increase in number and can destroy even more cancer cells.

Approved CAR T-cell Therapies

Currently, there are two CAR T-cell therapies approved for use in the United States. One is for advanced or recurrent acute lymphoblastic leukemia in children and young adults. The other is for certain types of advanced or recurrent large B-cell lymphoma. This type of lymphoma is one of several types of non-Hodgkin's lymphoma. This technique has shown very encouraging results in clinical trials against these cancers. In many patients the cancer could not be found after treatment, although it’s not yet clear if these therapies will result in a long-term cure. In some patients the CAR T-cells seem to go away after the cancer has been in remission for a while and researchers are studying whether those patients have a higher risk of their cancer coming back. Researchers are also studying long-term side effects of this kind of treatment. Other CAR T-cell therapies to treat different types of cancer are being studied and are currently only available in clinical trials. For more information, see What's New in Cancer Immunotherapy Research?

CAR T-cell Side Effects

Some people have had serious side effects from this treatment, especially as the CAR T-cells multiply in the body to fight the cancer. Serious side effects can include very high fevers  and dangerously low blood pressure in the days after it’s given. This is called cytokine release syndrome, or CRS. Doctors are learning how to manage these side effects. Other serious side effects include neurotoxicity or changes in the brain that cause confusion, seizures, or severe headaches. Some patients have also developed serious infections, low blood cell counts and a weakened immune system. These side effects can be life threatening and it is important for patients to know what to watch for and to tell the cancer care team if any of these symptoms develop.

 

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: July 23, 2015 Last Revised: October 31, 2017

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