Research & Discovery > What Is CAR-T Cell Therapy? Exploring a Promising New Cancer Treatment

What Is CAR-T Cell Therapy? Exploring a Promising New Cancer Treatment

By Christine Tully Photography by Paul E. Najlis

Traditionally, physicians had three options to treat cancer: surgery, radiation therapy and chemotherapy. But a promising new alternative — chimeric antigen receptor-T cell therapy (CAR-T cell therapy) — has transformed treatment options for certain types of cancer, giving more patients hope.

What is CAR-T cell therapy?

CAR-T cell therapy is a form of immunotherapy in which a person’s T cells — white blood cells known as lymphocytes that are involved in the immune system response — are removed and genetically modified to produce chimeric antigen receptors (CARs). These CAR-T cells are then infused back into the patient’s bloodstream, where they target and destroy cancer cells.

As far as what cancers can be treated with CAR-T cell therapy, it is used primarily for blood cancers like multiple myeloma, leukemias and lymphomas. Five years ago, patients with blood cancer faced a 10% to 15% survival rate. Today, survival rates are around 40% and improving. Even with that progress, Mohamed Kharfan Dabaja, M.D., M.B.A., a hematologist and director of the Blood and Marrow Transplantation and Clinical Cellular Immune Therapies program at Mayo Clinic in Florida, says “the job is not done yet.”

"We need to continue to bring new therapies, and to understand not only why it is not working on a certain patient but also why it is in others,” he says. "That will bring new knowledge about how to improve treating blood cancers.”

How does CAR-T cell therapy work?

CAR-T cell therapy is a complex process that harnesses the power of a person’s own immune system by engineering T cells to recognize and destroy cancer cells. The process can take several weeks, and patients are monitored as frequently as every month after receiving the therapy until their health improves and there are fewer signs of disease.

STEP 1

COLLECTION

T cells are removed from a patient’s blood through an apheresis machine in a process known as “leukapheresis.” The rest of the blood is then returned to the patient’s body.

STEP 2

ACTIVATION

The CAR-T cells can identify and attach to distinct marker proteins on the surface of cancer cells. This activates their ability to locate and destroy a patient’s cancer.

STEP 3

ALTERATION

T cells are genetically altered by scientists using a lentiviral vector, a method by which genes can be inserted, modified or deleted in organisms. This modification enables the T cells to generate surface receptors, known as chimeric antigen receptors (CARs), which allow them to change the activity of a cell.

STEP 4

REPLICATION

Scientists replicate millions of identical copies of these CAR-T cells in the laboratory.

STEP 5

PREPARATION

In preparation for the CAR-T cell infusion, the patient may undergo chemotherapy to suppress their other immune cells — giving the CAR-T cells a better chance to proliferate and fight the specific cancer cells.

STEP 6

INFUSION

The patient receives an infusion of CAR-T cells.

STEP 7

OBSERVATION

The patient is monitored closely for up to three months after the CAR-T cell infusion, helping to identify potentially life-threatening complications early.

The next generation of cancer therapy

Mayo Clinic researchers are searching for ways to expand CAR-T cell therapy to more types of cancers. Next-generation CAR-T cell therapy trials are expanding beyond blood cancers into new tumor types and exploring new techniques, such as using donor T cells or other immune cells to destroy cancer.

In 2019, a multisite clinical trial of CAR-T cell therapy was offered as part of Mayo Clinic’s CAR-T Cell Therapy Program, which enrolled 117 patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma.

CAR-T Cell Therapy
Patient Spotlight

Jon and Carolyn Stahlecker always dreamed of moving to the countryside. But they weren’t sure if they would ever have the chance to fulfill their dream. In 2007, Jon was diagnosed with chronic lymphocytic leukemia (CLL) — a cancer that currently has no cure.⁠ ⁠

Despite multiple rounds of chemotherapy, Jon’s cancer kept coming back. Then, in June 2019, Jon received a call saying he would be a strong candidate for a new clinical trial. CAR-T cell therapy sent Jon’s cancer into complete remission.⁠ ⁠

The research study, documented in The Lancet, found that 18% of participants who had relapsing CLL and no longer responded to treatments such as chemotherapy or BTK inhibitor drugs experienced complete remission after a single infusion of standard CAR-T cell therapy. The results are encouraging. So far, many patients are not seeing relapses — even years later — like Jon Stahlecker, who is now living his life to the fullest after battling CLL for more than a decade.

The Food and Drug Administration recently approved this new CAR-T cell therapy for relapsed or refractory CLL and small lymphocytic lymphoma — thanks in part to Mayo Clinic’s work on this multisite trial.

Additionally, Mayo Clinic has begun biomanufacturing some CARs on-site, which may help better tailor treatment to a patient’s individual needs. The hope is to provide another opportunity for patients whose cancers don’t respond to conventional, commercially approved CAR-T cell therapy options.