An Overview of CAR-T Therapy

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Chimeric antigen receptor T-cell treatment, also called CAR-T therapy, is a type of adoptive cell transfer therapy used for treating certain kinds of cancer. Normally, T-cells fight cancer cells to prevent them from multiplying and causing disease. CAR-T treatment and most of its research has been focused on blood cancers like leukemia and lymphoma. Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) are the first CAR-T drugs approved by the U.S. Food and Drug Administration (FDA). Note there are other types of adoptive cell transfer therapies besides CAR-T.

Immunotherapy is a process that uses a person’s own immune cells to treat diseases. CAR-T involves multiple steps in which immune cells are removed from a person’s own body, genetically modified in a laboratory using the drug, and then placed back into the body to fight cancer.

If you are having CAR-T therapy, you may also need to take immunosuppressive chemotherapeutic medication to help optimize the effects of your treatment.

Indications

The medications used in CAR-T treatment are approved for the treatment of specific tumors in certain age groups. 

  • Kymriah (tisagenlecleucel): Approved for the treatment of refractory or relapsing acute lymphoblastic leukemia (ALL) for children and adults up to age 25. It is approved for the treatment of relapsing non-Hodgkin lymphoma or non-Hodgkin lymphoma that is refractory to at least two other kinds of treatment.
  • Yescarta (axicabtagene ciloleucel): Approved for treatment of adults who have B-cell lymphoma, including relapsed large B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma that has relapsed or is refractory after at least two treatments with systemic therapy.

In the research setting, there are a number of clinical trials investigating the effects of these approved CAR-T medications, as well as other CAR-T drugs that are still in the development phase.

Experimental trial protocols may permit the use of CAR-T drugs for other indications and ages besides those for which Kymriah and Yescarta are approved.

How CAR-T Immunotherapy Works 

This treatment method works by using the medications to genetically modify a person’s immune cells. The immune cells are removed from a person’s blood and altered before being placed back into the body.

After the modified immune cells are re-infused, the changes they have undergone cause them to bind to the cancer cells. The immune cells then multiply within the body and work to help eradicate the cancer. 

White blood cells (WBCs) include two major types of immune cells: T-cells and B-cells. Normally, T-cells fight cancer cells to prevent them from multiplying and causing disease.

CAR-T drugs work by genetically modifying the body’s own T-cells cells so they will develop a protein—chimeric antigen receptor (CAR)—on their exterior surface. This is a genetically engineered combined (chimeric) receptor inserted into the T-cells by which the T-cells are able to recognize and destroy directly and more effectively the tumor cells.

This receptor binds to a protein (typically described as an antigen) on the surface of the cancer cells. For example, some types of immune cancers that are caused by B immune cells have an antigen on their surface called CD19. Both Kymriah and Yescarta generically modify T-cells to produce anti-CD19 receptors.

Gene Editing 

The genetic modification of the T-cells is described as gene editing. Kymriah and Yescarta use a lentiviral vector to insert the anti-CD19 gene into the T-cells. Even though a virus is used to insert genetic material into the DNA of a target cell, the process is controlled and it won’t cause a viral infection.

Another gene editing tool, clustered regularly interspaced short palindromic repeats (CRISPR), uses a type of technology that allows precise insertion of DNA into the genes of the target cell. Some CAR-T research uses CRISPR rather than retroviral vector gene editing.

Limitations

In general, CAR-T is more effective for the treatment of blood cancers than other types of cancer. With blood cancer, like lymphoma and leukemia, cancer cells tend to circulate throughout the body.

The modified T-cells can more easily locate and bind to circulating cancer cells than to tumor growths, which may have many cancer cells enclosed deep within a tumor where the T-cells can’t reach.

Procedure

CAR-T treatment involves several steps. First, T-cells are collected through leukapheresis, which is the removal of WBCs from the blood. This can take about two to four hours. A needle is placed in the vein, and after the WBCs are removed and saved through a filtering technique, the blood is placed back into the body through another vein.

Throughout this process, you will be monitored to make sure that your heart, blood pressure, and breathing are not negatively affected by the blood collection.

If you experience any side effects, be sure to tell your medical team so your procedure can be slowed down or adjusted as needed.

You should recover from this part of the procedure fairly quickly, and you will likely be discharged home on the same day.

Cell Preparation

The T-cells are sent to the laboratory, treated with the medication, and genetically altered to become CAR-T cells. The modified T-cells multiply in the laboratory for several weeks. You can expect to wait approximately four weeks after your cells are collected before your CAR-T cells are ready to be infused into your body. 

While you are waiting, you may undergo treatment with lymphodepletion chemotherapy to reduce your circulating immune cells. This can optimize the effects of the CAR-T cells. Your oncologist will explain any risks and side effects of the chemotherapy so you will know what to look out for.

Infusion

Your CAR-T cell infusion will be given intravenously (IV, in a vein) over several hours in a medical setting, such as an infusion center.

If you experience any complications or side effects, be sure to tell the team of providers who are taking care of you.

You will be monitored to make sure that your vital signs—such as your blood pressure, temperature, and heart rate—are normal before you will be discharged to go home on the day of your infusion.

Recovery

Studies have shown a high rate (over 70%) of remission (cancer free) in response to CAR-T. Because it is a relatively new type of therapy, long-term outcomes are not known.

If you have a good outcome, it is still important that you follow up with your oncologist so that you can continue to have routine monitoring to see if there are any signs of cancer recurrence.

Side Effects

A number of side effects can develop as a result of CAR-T treatment. The most common are cytokine release syndrome (CRS) and neurological toxicities, and these side effects have been described in over 80% of people who have CAR-T therapy. Nevertheless, experts who treat patients with CAR-T therapy are prepared to recognize the signs of these side effects and to treat them.

What to watch out for:

  • CRS: This can manifest with fevers, chills, nausea, vomiting, diarrhea, dizziness, and low blood pressure. It may begin a few days after infusion, and it can be treated with Actemra (tocilizumab), an immunosuppressive drug that is approved for treatment of CRS.
  • Neurological toxicities: This can begin within a week after the infusion and may include confusion, changes in consciousness, agitation, and seizures. Urgent treatment is necessary if any of these side effects develop.

There is some variation in the incidence of side effects of the two approved CAR-T drugs, but they are generally similar.

A Word From Verywell

Cancer is treated with several different methods, and sometimes with a combination of therapies. CAR-T therapy uses genetic modification to help fight cancer. It is one of the newer approaches in cancer treatment, and, while there are still only a few approved indications currently, there is a great deal of ongoing research into wider application of this technology for cancer treatment.

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