CAR T-Cell Therapy for Cancer

CAR T-cell therapy is a standard treatment for several types of advanced blood cancers, including some forms of leukemia, lymphoma, and multiple myeloma. Treatment with CAR T-cell therapy has led to long-lasting remissions and cures in many children and adults with advanced, treatment-resistant cancers, although not all people’s cancer responds to the treatment, and among those whose cancer does respond, how long it is kept in check varies.

The CAR T-cell therapies currently approved by the U.S. Food and Drug Administration are made from patients’ own immune cells, which is why these treatments are sometimes called “living drugs.”

What’s a T cell?

There are many types of immune cells. B cells, for example, make the antibodies our immune system needs to respond to dangerous bacteria and viruses. Dendritic cells are like a 24-7 security system, constantly scanning the body for threats and alerting other immune cells, including T cells, when one is detected.

There are several different types of T cells, including those whose primary function is to kill infected cells and cancer cells. To do their job, these T cells rely on special proteins, called receptors, that sit on their surface. Like a tiny crab on a beach pinching your toe, these receptors allow T cells to latch on to specific molecules, called antigens, on the surface of cancer cells.

But T cells aren’t perfect and cancer cells can often avoid detection, allowing them to form tumors. Once cancers reach that point, they have different ways of masking their presence or fending off T cell attack.

What’s CAR T-cell therapy?

CAR T cells are T cells that have a special receptor that can grab onto specific molecules, called antigens, found primarily on cancer cells. With CAR T-cell therapy, hundreds of millions of these T cells are infused into patients to treat their cancer.

The special receptor on the T cells is a chimeric antigen receptor, or CAR. The T cells used in this treatment come from patients. In other words, each CAR T-cell therapy is specifically made for each patient, using their own T cells.

How are CAR T-cell therapies made?

Making CAR T-cell therapies is complicated. Generally speaking, the process involves:

• collecting blood from the patient and separating out the T cells
• genetically engineering the T cells to produce CARs that are designed to target a specific antigen found on the surface of cancer cells
• growing (or “expanding”) the engineered T cells into the hundreds of millions
• sending the final treatment back to the hospital where the patient is being treated
• infusing the CAR T cells into the patient

Currently, this process—from initial cell collection to final infusion—typically takes 2 to 4 weeks.

What are the side effects of CAR T-cell therapies?

The most common and serious side effect is cytokine release syndrome, or CRS. This side effect occurs in nearly 90% of people treated with CAR T-cell therapy. It can cause very high fevers, joint pain, and extreme fatigue, among other symptoms. Care teams carefully monitor for CRS and in most patients its severity and duration can be well managed.

Another less common but serious side effect is called ICANS, a group of neurological symptoms that range from confusion and speech issues to swelling in the brain. Similar to CRS, ICANS can be well managed and usually reversed with available treatments.

Are new CAR T-cell therapies being developed?

Researchers are testing many new CAR T-cell therapies, including those that target antigens commonly found on so-called “solid tumors,” such as aggressive forms of brain and breast cancer.

Many different types of experimental CAR T-cell therapies are being studied. For example, researchers are intensively studying CAR T-cell therapies that involve delivering the genetic instructions for making CARs to T cells while they are still in the body.

This and many other new CAR T-cell therapy approaches are still experimental and, although many are being tested in clinical trials, they cannot be used in everyday cancer care.