CAR T-cell Therapy and Its Side Effects

Your immune system works by keeping 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. Chimeric antigen receptor (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 immune effect cell therapy.

The immune system recognizes foreign substances in the body by finding proteins called antigens on the surface of those cells. Immune cells called 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 if your immune cells do not have the right receptors, they cannot attach to the antigens and help destroy the cancer cells.

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.

The process for CAR T-cell therapy can take a few weeks.

First, white blood cells (which include T cells) are removed from the patients 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 line, and then put back into the bloodstream through the other line, after the white blood cells have been removed. Sometimes a special type of IV line is used called a central venous catheter, that has both IV lines built in. The patient will need to stay still for 2 to 3 hours during the procedure. Sometimes calcium levels can drop during leukapheresis, which can 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, 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 the large number of CAR T cells needed for this therapy.

Once enough CAR T cells have been made, 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, the patient might be given chemotherapy to help lower the number of other immune cells. This gives the CAR T cells 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.

CAR T cell therapy is FDA approved for some kinds oflymphomas, and for certain patients with relapsed or hard to treat leukemia. Many clinical trials are underway with the hope of treating even more patients. One problem with some types of cancer is that they dont have the same antigens for the CAR T cell to work with because the proteins are inside the cells, not on the cell surface. This may mean that the CAR T cell needs a special armor to be able to get into the cell to work. More research is needed to study this.

The CAR T-cell therapies currently approved are:

Some people have had serious side effects from this treatment, especially as the CAR T cells multiply in the body to fight the cancer. As CAR T cells multiply, they cause massive amounts of chemicals called cytokines to be released into the blood. Serious side effects of this release can include very high fevers and dangerously low blood pressure in the days after treatment is given. This is called cytokine release syndrome, or CRS. Even though it can be a scary side effect, it's important to remember that it means the CAR T cells are working and doctors have learned how to expect it and treat it.

Other serious side effects include neurotoxicity or changes in the brain that cause swelling, confusion, seizures, or severe headaches.

One other problem is that the CAR T cells can kill off some of the good B cells that help fight germs, so the patient may be at risk for infection.

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CAR T-cell Therapy and Its Side Effects