T-cells are powerful weapons in the body's fight against disease. These lymphocytes not only attack viruses and parasites, but they adapt to recognize specific threats should they reappear. But sometimes, T-cells need help, especially when it comes to fighting cancer. Some of that help has come in the form of immunotherapy—drugs that give T-cells added tools to help them seek out and kill cancer cells. Checkpoint inhibitor drugs, for instance, are designed to block deceptive signals that prevent T-cells from recognizing cancer. Now, researchers have figured out a new way to empower some T-cells, by re-engineering them with an extra gene designed to allow them to identify and attack specific cancer cells. The development is considered groundbreaking because it marks a new approach to helping the body fight hard-to-treat cancers.
Calling it “a historic action,” the U.S. Food and Drug Administration (FDA) endorsed the approach this week, when it approved a new type of immunotherapy—called CAR T-cell therapy or gene therapy—that give T-cells another weapon against relapsed or refractory acute lymphoblastic leukemia (ALL) in patients aged 25 and younger. "This is an exciting new development for the treatment of a patient population with limited treatment options," says Dr. Maurie Markman, President of Medicine and Science for Cancer Treatment Centers of America® (CTCA).
The approved therapy, tisagenlecleucel (Kymriah®), uses modified immune cells called chimeric antigen receptor (CAR) T-cells. (A chimera is a mythical beast with a head, body and tail of different animals.) These cells are customized for each patient, using the patient’s own T-cells, removed from the bloodstream in a process called apheresis. The cells are then sent to a lab, where they are modified with a gene containing a protein that directs the T-cells to target leukemic B-cells with a specific antigen (CD19) on their surface. The super-charged T-cells are reproduced by the billions, then infused back into the patient. The entire process takes about three weeks. "We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer," FDA Commissioner Dr. Scott Gottlieb said in a statement.
According to the FDA, tisagenlecleucel may cause severe side effects, including cytokine release syndrome (CRS), a toxic flood of cytokines that may result in flu-like symptoms, high fever, life-threatening neurological side effects and/or other serious conditions. The FDA is requiring hospitals that use the treatment to be certified and trained to recognize and manage CRS. In conjunction with the tisagenlecleucel approval, the FDA expanded the approval of the drug tocilizumab (Actemra®) to treat CRS and specified that CAR T-cell therapy should not be administered unless tocilizumab is immediately available. Also, because CD19 is found on healthy B-cells, tisagenlecleucel may also destroy those cells, creating an increased risk of infections.
One of CAR T-cell therapy's earliest patients is Emily Whitehead, who was 6 years old when she was treated at Children's Hospital of Philadelphia in a story featured in the PBS series Cancer: The Emperor of all Maladies. Emily was near death when she was given a dose of CAR T-cells that were modified with a virus derived from the human immunodeficiency virus (HIV). Emily is now 12 and has no sign of active disease. She appeared with her parents at the FDA hearing on the treatment. Emily had ALL, a type of cancer in which the bone marrow produces too many defective lymphocytes.
In many cases, ALL is treated with positive outcomes with chemotherapy, stem-cell transplants or targeted therapy. But in some cases, these treatments do not produce sufficient results, and the disease becomes highly resistant. In one clinical trial, 52 of 63 patients (82 percent) with relapsed or refractory B-cell ALL showed no sign of the disease within three months of being treated with tisagenlecleucel. Dozens of clinical trials are underway to determine if CAR T-cells may be an option to treat other blood cancers, including lymphoma and other forms of leukemia, as well as cancers with solid tumors, such as brain and breast cancer. "Additional research efforts will be required to further define the role of this quite novel approach to cancer management," Dr. Markman says.
Learn more about hematologic oncology, an area of cancer care dedicated to diagnosing and treating blood cancers.