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CAR T-cell therapy is a personalized form of immunotherapy that trains your own immune cells to recognize and destroy cancer. It can be a powerful option for treating certain hard-to-treat blood cancers, especially when other treatments are no longer effective.

What is CAR T-cell therapy?

CAR T-cell therapy or CAR T therapy (short for chimeric antigen receptor T-cell therapy) is a type of cell-based gene therapy that alters the genes in a person’s T cells (a type of white blood cell) to help them attack cancer cells.

This type of treatment can be helpful in treating some types of cancer, even when other treatments are no longer working.

How does CAR T-cell therapy work?

To understand how CAR T-cell therapy works, it helps to know how the immune system uses receptors on T cells to find antigens on cells it sees as foreign. This connection is key to how CAR T cells are made to target cancer.

How immune receptors and foreign antigens interact

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 (sometimes called T lymphocytes) 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 a lock can only be opened with the right key, each foreign antigen has a unique immune receptor that can bind to it.

Cancer cells also have antigens, but if your immune cells don't have the right receptors, they can't attach to the antigens and help destroy the cancer cells.

How CAR T-cell therapy changes your T cells

In CAR T-cell therapy, T cells are taken from your blood and genetically changed in the lab to have a receptor called a chimeric antigen receptor (CAR) on their outer surface. This helps the T cells attach to a specific cancer cell antigen. The CAR T cells are then returned to your blood.

Since different cancers have different antigens, each CAR is made for a specific cancer's antigen. This means CAR T-cell therapies are monoclonal—each is designed to recognize one target.

 For example, in certain kinds of leukemia or lymphoma, the cancer cells have an antigen called CD19. Many of the CAR T-cell therapies to treat these cancers are made to attach to the CD19 antigen and will not work for a cancer that doesn’t have the CD19 antigen.

This is different from polyclonal cellular therapies such as tumor infiltrating lymphocyte (TIL) therapy that can recognize multiple antigens.

Which cancers can be treated with CAR T-cell therapy?

CAR T-cell therapies are approved by the US Food and Drug Administration (FDA) to treat some kinds of lymphomas and leukemias, as well as multiple myeloma. CAR T-cell therapy is typically used after other types of treatment have been tried.

Examples of CAR T-cell therapies currently approved include:

• Tisagenlecleucel, also known as tisa-cel (Kymriah)
• Axicabtagene ciloleucel, also known as axi-cel (Yescarta)
• Brexucabtagene autoleucel, also known as brexu-cel (Tecartus)
• Lisocabtagene maraleucel, also known as liso-cel (Breyanzi)
• Idecabtagene vicleucel, also known as ide-cel (Abecma)
• Ciltacabtagene autoleucel, also known as cilta-cel (Carvykti)
• Obecabtagene autoleucel, also known as obe-cel (Aucatzyl)

Many other CAR T-cell therapies (and similar types of treatment) are now being studied in clinical trials, in the hope of treating other types of cancer as well.

What is it like to have CAR T-cell therapy?

Getting CAR T-cell therapy is quite different from other types of immunotherapy treatment. It involves:

• Having the T cells collected from your blood, usually in 1 or more outpatient procedures
• Waiting several weeks for them to be modified and multiplied in the lab
• Getting the CAR T-cell infusion and being monitored closely, sometimes in the hospital for 1-2 weeks

Collecting the T cells

First, white blood cells (which include T cells) are removed from your blood using a procedure called leukapheresis. Two IV lines are used:

• Blood is removed through one line
• The white blood cells are separated out using a special machine (apheresis)
• Then the remaining blood is put back into your body through the other line.

Sometimes a special type of IV line called a central venous catheter is used, which has both IV lines built in.

This process typically takes several hours, and you will need to stay seated or lying down during the procedure. It might need to be repeated another day or more until enough cells are collected.  

Sometimes blood calcium levels can drop during leukapheresis, which can cause numbness and tingling or muscle spasms. This can be treated by replacing the calcium, which may be given by mouth or through an IV.

Waiting for the CAR T cells to be made

After the white cells are removed, they are frozen and sent to a special cell therapy lab. From there they are genetically changed to have the specific chimeric antigen receptor (CAR) on the surface of the T cell. This makes them CAR T cells.

These cells are then grown and multiplied in the lab. It can take several weeks to make the large number of CAR T cells needed for this therapy.

Receiving the CAR T-cell infusion

Once enough CAR T cells have been made, steps will be taken to get you ready to receive them.

A few days before the CAR T-cell infusion, you will likely be given a short course of chemotherapy to help lower the number of other immune cells in your body. This gives the CAR T cells a better chance to get activated to destroy cancer without your body attacking them. This chemotherapy is usually not very strong because CAR T cells work best when there are still some cancer cells to attack.

A few days later, you will receive your CAR T cells as an infusion (through an IV) into your blood. This usually takes between 30 to 60 minutes, but can last longer. You’ll be monitored for any signs of a reaction. Once the infusion is complete, your doctor will tell you when you can return home.

For several weeks after the infusion, you’ll get regular checks at the hospital. This will help your doctor identify any problems or reactions to the therapy as soon as possible.

Once the CAR T cells start binding with cancer cells, they start to increase in number and can help destroy even more cancer cells.

Side effects of CAR T-cell therapy 

CAR T-cell therapy can be very effective against some types of hard-to-treat cancers, but it can also sometimes cause serious or even life-threatening side effects. Because of this, it needs to be given in a medical center specially trained in its use, and you will need to be watched closely for several weeks after getting the CAR T cells.

Cytokine release syndrome (CRS)

As CAR T cells multiply, they can release large amounts of chemicals called cytokines into the blood, which can ramp up the immune system. Serious side effects from this release can include:

• High fever and chills
• Trouble breathing
• Severe nausea, vomiting, and/or diarrhea
• Feeling dizzy or lightheaded
• Headaches
• Fast heartbeat
• Feeling very tired

As doctors are gaining more experience with CAR T-cell therapy, they are learning how to recognize CRS early, as well as how to treat it.

Nervous system problems

This treatment can sometimes have serious effects on the nervous system, leading to a condition called immune effector cell-associated neurotoxicity syndrome (ICANS). This can result in symptoms such as:

• Headaches
• Changes in consciousness (awake easily or hard to awaken)
• Confusion or agitation
• Seizures
• Shaking or twitching (tremors)
• Trouble speaking and understanding
• Loss of balance

Because of the risk of these side effects, you’ll likely be told not to drive, operate heavy machinery, or do any other potentially dangerous activities for at least 8 weeks after getting treatment.

Other serious side effects

Other possible serious side effects of CAR T-cell therapy can include:

• Allergic reactions during the infusion
• Abnormal levels of minerals in the blood, such as low potassium, sodium, or phosphorous levels
• A weakened immune system, with an increased risk of serious infections
• Low blood cell counts, which can increase the risk of infections, fatigue, and bruising or bleeding
• Increased risk of second cancers

If you are getting CAR T-cell therapy, it’s very important to report any side effects to your cancer care team right away, as there are often medicines that can help treat them.

How is CAR T-cell therapy paid for?

CAR T therapy is expensive. On average, the cost of the CAR T cells alone can range from $300,000 to $475,000 because of the complexity of how the cells are collected and made. This doesn’t include the costs of hospital admission, tests, procedures, and other expenses which can lead to the total cost being well over $500,000.

While Medicare and many commercial insurances do cover some of the costs of CAR T therapy, they usually don’t cover the full amount. The amount of coverage also varies between commercial plans. Medicaid coverage also varies and depends on your state of residence.

Before starting CAR T therapy, your care team will work with your insurance company to check what your policy covers. You will want to ask questions to learn as much as possible about the costs of cancer treatment. Be sure to talk with them about out-of-pocket costs including deductibles, co-payments as well as other medication costs. The CAR T center will also likely have a social worker, nurse navigator or financial coordinator to help with this process. They can talk with you about programs to help with expenses and help you access resources in your local community.