Frequently Asked Questions About CAR T-cell Therapy

What is CAR T-cell therapy?

CAR T-cell is a type of cellular therapy. We take immune cells out of a patient’s body, and then we modify these cells so that they can target and kill cancer cells. Then we reinfuse these cells into the patient. The cells go into the patient, find their target on the cancer cell surface and kill those cells.

How is that different from chemotherapy?

When you think of chemotherapy drugs, they are not aimed at specific targets on the cancer cell. The problem then is that they kill other, healthy cells in the body. Other organs and tissue are damaged by the chemotherapy, rather than just the cancer cells. CAR T-cell therapy is more specific to the cancer cells because they are trained to target a particular protein on the surface of the cancer cell.

Who qualifies for this therapy?

adult patients with diffuse large B-cell lymphoma
Children and young adults up to age 25 with B-cell acute lymphoblastic leukemia

Both treatments are approved for those patients who have progressive disease after they get their first or second round of treatment. Usually these patients received initial chemotherapy, and maybe they went into remission but then they relapsed afterward, or they didn’t respond to the chemotherapy at all.

Usually that relapse happens within six months, but it could happen several years down the road.

This is not something we would give a newly diagnosed patient. While this treatment looks promising, clinical trials have only looked at using this for patients with relapsed disease. We need more studies before knowing if it should be an option for newly diagnosed patients. For now, it’s still the standard of care to give those patients chemotherapy initially, and then if they relapse or don’t respond to chemo then they can get this CAR T-cell product.

How does it work?

After a patient is evaluated, he or she undergoes a process called apheresis. The patient is connected to a machine that’s a little bit like a dialysis machine for a few hours. The machine siphons the blood out of the patient, separates out the T-cells, and then pumps the blood back into the patient.

We then send the T cells to the pharmaceutical company, where they modify these cells by forcing them to produce a certain receptor (chimeric antigen receptor) on the cell surface that is targeted to a marker on cancer cells. The modified CAR T-cells are then sent back to us at the Rogel Cancer Center.

Patients are given back their modified T cells by intravenous infusion. These cells begin to multiply in the bloodstream, and the receptor the cells have produced attaches to a surface marker that is found mainly on the cancer cells, causing a reaction where the immune cell kills the cancer cells.

What does a patient need to know going into this?

CAR T-cell therapy can have some severe side effects, and that’s why we monitor patients very closely. We ask that patients live within a 60-mile radius of the University of Michigan for the first couple of months after they get the therapy because we are going to be seeing them very frequently.

One of the major side effects is something called cytokine release syndrome. This presents like the patients have an infection. They can develop high fevers, a high heart rate and low blood pressure. Some patients will need to go to the intensive care unit for a higher level of care. That is why we monitor them very carefully in the hospital for the first two to three weeks after they receive the CAR T-cell therapy.

Interestingly enough, what we saw was that developing the syndrome actually correlated with responding well to the treatment. So it is a sign that the patient is responding well to the CAR T-cell therapy.

What distinguishes University of Michigan as a destination for CAR T-cell therapy?

We have had a lot of experience with CAR T-cell therapy and cellular therapy in general. We have treated patients with CAR T-cell therapies here, and we have a lot of people on our staff who have experience from different centers in treating T-cell patients. I trained at the National Cancer Institute where a lot of these cells were actually developed and took care of many patients there who had received CAR T-cells.

University of Michigan has a great infrastructure. We have a large and active blood and marrow transplant program. We also have a lot of experience managing the various side effects that can occur from this therapy.

The cancer center has also established a clinical cellular therapy program with a multidisciplinary team of experts that manages these patients. The team has developed clinical practice guidelines and standard operating procedures and meets weekly to specifically discuss the patients in our care who are receiving CAR T-cell therapy.

Is this just the beginning of what’s to come with CAR T-cell therapy?

There are a number of CAR T-cell therapies targeting various cancer cell targets and trials in pancreatic cancer, lung cancer, sarcoma, melanoma -- all sorts of different cancers in addition to leukemia and lymphoma. These are currently clinical trials, but we expect to see these become approved as a standard of care in the coming years.