What Is CAR T-Cell Therapy? The Treatment Making Headlines, Explained

A drug that is alive

Most cancer drugs are molecules. They are given, they act, they are cleared from the body.

CAR T-cell therapy is different in kind. The product is a population of living cells taken from the patient, altered, and returned. Once inside, those cells keep dividing. One researcher quoted by NCI calls it "a living drug", and the phrase is literal rather than promotional.

That is why a single infusion can be the whole treatment, and also why the risks are unlike a drug's.

What a CAR actually is

T cells are the immune system's main killers of infected and damaged cells. They already know how to destroy a target. What they often cannot do is recognize a cancer cell as a target.

A chimeric antigen receptor, or CAR, supplies that recognition. NCI describes it as a protein that spans the cell membrane, with part outside and part inside.

The outside part is built from fragments of laboratory-made antibodies. These fragments determine what the receptor binds to, which is an antigen, a protein found on cancer cells and sometimes on normal cells too.

The inside part carries signaling and co-stimulatory domains. When the receptor grabs its target, these send instructions into the T cell that tell it to kill and to multiply.

"Chimeric" refers to the splice: an antibody's recognition end joined to a T cell's action end. Our page on CAR T-cell therapy goes further into the design.

The weeks between the blood draw and the infusion

The timeline is the part patients least expect, and NCI sets it out plainly.

Blood is collected and T cells are separated from it. The cells travel to a manufacturer's laboratory, where they are genetically engineered to make the receptor. They are then grown, or expanded, until there are hundreds of millions of them. The finished product returns to the hospital and is given as a single infusion.

NCI states the whole process currently takes about three to five weeks.

Before the infusion, patients receive chemotherapy, and sometimes radiation, to reduce their existing immune cells. NCI explains the reason: clearing space helps the transferred cells work.

Waiting weeks matters when a cancer is advancing quickly. It is one of the practical limits on who can receive this treatment.

Which cancers, and which products

FDA approved the first CAR T-cell therapy in 2017, tisagenlecleucel (Kymriah), for children with acute lymphoblastic leukemia that had relapsed.

That approval rested on trials showing the treatment cleared leukemia in most of those children. Longer follow-up has shown many of them surviving years without the cancer returning. NCI describes them as appearing cured. It is now a standard option for children whose leukemia has come back after several other treatments.

NCI's current list names seven CAR T-cell therapies approved by FDA for blood cancers:

• Axicabtagene ciloleucel (Yescarta).
• Brexucabtagene autoleucel (Tecartus).
• Ciltacabtagene autoleucel (Carvykti).
• Idecabtagene vicleucel (Abecma).
• Lisocabtagene maraleucel (Breyanzi).
• Obecabtagene autoleucel (Aucatzyl).
• Tisagenlecleucel (Kymriah).

The approvals since 2017 are all for adults with blood cancers, including several lymphomas and multiple myeloma. NCI quotes one of its own investigators on advanced lymphoma. People whose disease could not be controlled by standard treatment were once close to untreatable. That is no longer so. Our pages on lymphoma and leukemia cover those diseases.

What goes wrong

NCI is explicit that CAR T-cell therapy does not work for everyone and can cause serious harm.

The characteristic complication is cytokine release syndrome. Cytokines are signaling substances the immune system uses. When the transferred cells activate, they and other immune cells release large amounts at once.

NCI lists the effects: fever, nausea, headache, rash, rapid heartbeat, low blood pressure and trouble breathing. Most people get a mild version. In some it is severe or life-threatening, and there are treatments to control it.

The second concern is neurological. Confusion is the symptom most often mentioned, and effects can be severe.

There is a third, structural problem. CAR T cells are designed to recognize proteins found on cancer cells, but those proteins are rarely unique to cancer. When the cells attack normal tissue carrying the same antigen, organ damage can follow.

Because of all this, CAR T-cell therapy is given at experienced centers with the staff and drugs to manage these reactions quickly.

Why solid tumors have been harder

Almost everything above concerns blood cancers. NCI states that CAR T-cell therapy has been studied in solid tumors including breast and brain cancers, but that its use there remains experimental.

A related cell therapy has crossed that line. Lifileucel (Amtagvi) uses tumor-infiltrating lymphocytes. These are immune cells taken from inside a person's own tumor, rather than engineered ones. FDA has approved it for melanoma. It is the first cell therapy approved for a solid tumor.

When to get checked

CAR T-cell therapy treats cancers already diagnosed, most of them blood cancers with no screening test. Symptoms are how they are found. Ask a doctor about:

• A lymph node in the neck, armpit, groin or abdomen that stays swollen for more than a few weeks and is painless.
• Fever with no known cause, or drenching night sweats.
• Weight loss you cannot explain.
• Tiredness that rest does not fix.
• Bruising or bleeding easily, or infections that keep returning.
• Bone pain that does not shift.

None of these means cancer on its own. They mean a blood count and an examination are reasonable next steps.

What this does not mean

A living drug is not a universal one. Every approved CAR T-cell therapy targets a specific antigen on a specific group of blood cancers.

An approval is not a guarantee of benefit. NCI's own summary says these treatments do not work for everybody, and the trials behind them measured eliminating cancer "for a time" in many patients.

And headlines about cures describe a subset. NCI uses the phrase "appear to be cured" carefully, about children with relapsed leukemia followed for years. It is a real observation about some people, not a description of the treatment as a whole. Our page on immunotherapy puts CAR T alongside the other approaches.

Sources

• NCI, CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers — https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
• NCI, T-cell Transfer Therapy — https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/t-cell-transfer-therapy
• NCI, Immunotherapy to Treat Cancer — https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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