How CAR-T Therapy Can Treat Cancer

RegMedNet on how the immunotherapy helps some patients recover from leukemias, lymphomas, and myeloma.

CAR-T (chimeric antigen receptor T cell) therapy is one of the newest types of immunotherapy on the cancer scene. The therapy modifies cancer patients’ T cells to make their immune systems better at identifying and destroying cancer cells. Although the therapy runs the risk of severe side effects, it has cured patients where other treatments have been unsuccessful.

Here, RegMedNet explains how CAR-T therapy works as a cancer treatment, the risk of cytokine release syndrome associated with the therapy, the support that patients receive after the treatment, and the cancers that the U.S. Food and Drug Administration (FDA) has approved CAR-T treatments for.

How Does CAR-T Therapy Work as a Cancer Treatment?

Most patients who undergo CAR-T therapy have already received a cancer treatment that hasn’t been effective. Previous cancer treatments often weaken T cells, which means they may not be as healthy when the patient undergoes CAR-T therapy. To collect T cells that are as healthy as possible, a clinician may collect the patient’s T cells during a pause in their treatment.

Apheresis

Patients receive their CAR-T treatment at a specialized center. First, a clinician collects some of the patient’s T cells through a process termed apheresis. They circulate the patient’s blood through a machine that filters out T cells and returns the rest of the blood to the patient. This is the most difficult part of the process for some types of cancer, and some patients aren’t eligible for the therapy for this reason.

Manufacturing CAR-T Cells

Next, a laboratory team modifies the T cells so they become CAR-T cells. This process can take a few weeks. When manufacturing CAR-T cells, a laboratory team adds a chimeric antigen receptor to each T cell’s surface. A chimeric antigen receptor comprises three proteins: a protein that will recognize antigens on the cancer cell and two proteins that will tell the T cell to activate when the first protein attaches to an antigen on the cancer cell. When a T cell combines with a chimeric antigen receptor, it becomes a CAR-T cell. These cells travel around the body looking for specific cancer cells that carry the antigen programmed into the CAR protein.

The laboratory team freezes the CAR-T cells and sends them back to the clinician. While the patient is waiting to receive their CAR-T cells, they can resume their regular cancer treatment.

Lymphodepletion

Before the clinician infuses the CAR-T cells into the patient’s bloodstream, the patient undergoes a short course of lymphodepletion (a type of chemotherapy) over two to three days. The lymphodepletion prevents the immune system from considering the CAR-T cells abnormal and rejecting them.

Infusing the CAR-T Cells in the Bloodstream

The clinician then thaws the CAR-T cells and infuses them in the patient’s bloodstream. This process is similar to a blood transfusion. Once in the bloodstream, the CAR-T cells circulate and find cancer cells. The CAR-T cells activate when they come into contact with an antigen on a cancerous cell. Activated CAR-T cells multiply, and their signaling proteins (cytokines) trigger other parts of the immune system to come to the site of the cancer cell. The activated T cells and cytokines cause significant inflammation of the cancer cell. If all of the cancer cells die, the cancer may disappear either temporarily or permanently.

How Big Is the Risk of Cytokine Release Syndrome?

CAR-T treatments can over-activate the immune system, which can cause cytokine release syndrome (CRS). This syndrome usually occurs within a few days and up to two weeks after CAR-T cell infusion. CRS can be harmful and can last days or weeks. The syndrome affects patients in different ways. While some only experience a fever, others experience low blood pressure and low oxygen levels. In the worst case, some patients need intensive care and may need machines to keep them alive.

However, medical advances have reduced the likelihood of CRS patients needing intensive care. The drug tociluzumab “turns off” a cytokine termed IL-6, which helps many patients recover. However, CRS is still a serious risk of CAR-T therapy.

Immune Effector Cell-Associated Neurotoxicity Syndrome

Cytokines can also affect the brain and cause a syndrome known as immune effector cell-associated neurotoxicity syndrome (ICANS). This syndrome can cause a range of additional symptoms, such as shaking, mild to severe confusion, memory loss, and occasionally, seizures. ICANS is almost always associated with CRS and usually occurs one to four weeks after CAR-T cell infusion. The syndrome is reversible, but some symptoms can take time to resolve.

What Support Do Patients Receive After CAR-T Therapy?

Specialists monitor patients in the weeks that follow their CAR-T therapy. After two to four weeks, patients are unlikely to develop severe complications. However, they must live near the treatment center to receive continued observations for approximately three months, at which point a clinician evaluates how effective the therapy has been.

This ongoing support is important because CAR-T cells kill all cells that they recognize, including normal cells. Therefore, most patients have a weak immune system for many months following the therapy. A weak immune system can leave the patient exposed to many rare infections that are usually seen in individuals who have severe immunodeficiencies. Therefore, individuals who are recovering from CAR-T treatments must be cautious and report any symptoms to their doctor.

Which Types of Cancer Has CAR-T Therapy Been Approved for?

With many clinical studies underway, approvals surrounding CAR-T therapies are rapidly shifting. Currently, clinicians use CAR-T therapies to treat multiple myeloma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, follicular lymphoma, and B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients up to the age of 25.

In March 2021, the FDA approved five new CAR-T treatments for these diseases. These treatments can cause serious side effects, so the FDA has only approved them for patients whose cancer has returned after at least one previous treatment (depending on the indication).

There is plenty of additional research underway into CAR-T therapies, including studies that examine how to make the therapies safer and studies that assess the efficacy of FDA-approved products for new indications and less treated patients. As this research develops, the cancer community hopes to see a bright future for CAR-T therapy and cancer patients.

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