CAR T-Cell Therapy: A New Front Against Cancer??>

CAR T-Cell Therapy: A New Front Against Cancer?

by Peter Jaret  

Despite decades of intensive research, cancer remains a formidable adversary—and a leading cause of death. So when researchers announce promising results from a revolutionary approach, it’s big news.

The treatment is called chimeric antigen receptor (CAR) T-cell therapy. In clinical trials, CAR T-cell therapy has emerged as an approach that can elicit long-lasting remission in hard-to-treat blood cancers. In 2017, the FDA approved the first CAR T-cell therapy for advanced recurrent B-cell acute lymphoblastic leukemia in children and young adults. Approval of treatments for certain forms of advanced or recurrent large B-cell non-Hodgkin lymphomas in adults soon followed. In both cases, the therapy is reserved for patients who don’t respond to first-line treatment (called refractory cancer) or whose cancer has returned (relapsed cancer).

In August 2019, Medicare announced it would cover much of the cost of CAR T-cell therapy, a signal that the novel approach has gone mainstream. That’s noteworthy, since the cost of treatment can easily reach $500,000 or more.

Attack of the T cells

CAR T-cell therapy is one of a group of new treatments, called immunotherapy, that harnesses the power of the body’s immune system to detect and destroy cancer cells. In this case, the treatment employs the body’s T cells, a type of white blood cell. T cells charge into action when they recognize foreign substances, or antigens, on cells. Antigens usually come from outside the body on the surface of bacteria, viruses, toxins, or other substances. Because cancer cells are produced by the body internally, they may not carry a foreign antigen on their surface, so T cells have trouble spotting them.

That’s where CAR T-cell therapy comes in. Using blood drawn from the patient, scientists isolate T cells and then genetically reengineer them in the lab to spot cancer cells, a process that can take several weeks. They do this by adding an artificial chimeric antigen receptor, which locks on to a matching molecule on cancer cells. Doctors must use an individual patient’s T cells so the immune system doesn’t reject them. Hundreds of millions of CAR T cells are created specifically for the individual patient, which is one reason why the treatment is so expensive. Because the therapy consists of living immune cells, it represents something truly revolutionary: a living drug.

Before the CAR T cells are infused into the bloodstream, the patient might need to undergo chemotherapy a few days before to reduce the number of other immune cells. This step makes room for the CAR T cells so they can better latch on to and destroy the cancerous cells. The infusion of CAR T cells typically takes under 30 minutes.

The clinical trial on which the approval of the adult lymphoma therapy was based produced strong results. In the study, led by the National Cancer Institute, 101 adult patients with an aggressive form of B-cell lymphoma underwent CAR T-cell therapy. Fifty-eight percent had a full response, meaning they were cancer-free after the treatment. The extent of cancer was partially reduced in another 25 percent. Without the therapy, it’s estimated that only 26 percent of patients would have achieved any type of response, with only 7 percent having a full response.

Unfortunately, three patients in the trial died from therapy-related complications. Because of the therapy’s risks, the FDA extended approval of CAR T-cell therapy only to facilities equipped to handle complications.

CAR T-cell therapy is relatively new, so researchers are still studying its long-term effects. In the clinical trial, 39 percent of the patients who had gone into remission remained cancer-free two years later.

The challenges of CAR T-cell therapy

As with all aggressive cancer therapies, CAR T-cell therapy has serious drawbacks. During early clinical trials, most patients developed an immune reaction to the infusion of CAR T cells. Called cytokine release syndrome, the reaction can range from mild flu-like symptoms to a life-threatening drop in blood pressure, a rapid heartbeat, and breathing problems. Fortunately, researchers have found ways to control the reaction with steroids or other powerful anti-inflammatory drugs.

Some patients experience neurological conditions such as mental confusion or seizures after undergoing therapy, but the effect is usually short-lived and reversible. Researchers are intensely studying this complication, called neurotoxicity.

Among other potential complications is B-cell aplasia, when B cells, which produce antibodies, die, leaving patients unprotected against infection. To counteract this effect, some patients must undergo immunoglobulin therapy.

It takes approximately two to three months for the immune system to recover from CAR T-cell therapy and no longer be susceptible to its risks.

On the horizon

So far, CAR T-cell therapy has been approved only for specific forms of leukemia and lymphoma. CAR T-cell therapy has already shown promise for treating multiple myeloma and other forms of leukemia. Cancers that grow as solid tumors, such as lung, breast, and prostate cancers, prove to be a more difficult target for this therapy.

Still, the success of therapy has jump-started intensive research around the world to refine the approach and to target other forms of cancer, with a number of clinical trials in the United States currently under way.

This article first appeared in the December 2019 issue of UC Berkeley Health After 50.