New treatment for leukemia points to a shift in the fight against cancer

T cells are powerful weapons in the body’s fight against disease. These lymphocytes not only attack viruses and parasites, but also adapt to recognize specific threats should they arise again. But sometimes T cells need help, especially when it comes to fighting cancer. Some of that help comes in the form of immunotherapy — drugs that give T cells extra tools to help them find and destroy cancer cells. Checkpoint inhibitor drugs, for example, are designed to block the false signals that prevent T cells from recognizing cancer. Now, researchers have discovered a new way to boost certain T cells, redesigning them with an additional gene designed to allow them to identify and attack specific cancer cells. This development is groundbreaking because it represents a new approach to helping the body fight hard-to-treat cancers.

The US Food and Drug Administration (FDA) called it a “historic measure” and approved the approach this week, when it approved a new type of immunotherapy, called CAR T-cell therapy or gene therapy, that gives T cells another weapon against it. Relapsing or refractory acute lymphoblastic leukemia (ALL) in patients 25 years of age or younger. “This is an exciting new development for treating patients with limited treatment options,” says Dr. Murray Markman, chief of medicine and science, Cancer Treatment Centers of America. ^® (CTCA).

T-cell customization

The approved treatment, tisagenlecleucel (Kymriah ^® ), uses modified immune cells called chimeric antigen receptor (CAR) T cells. (The illusion is a mythical monster with the head, body, and tail of different animals.) These cells are customized to each patient, using the patient’s own T cells, extracted from the bloodstream in a process called apheresis. The cells are then sent to a laboratory, where they are modified with a gene containing a protein that directs T cells to target leukemia B cells with a specific antigen (CD19) on their surface. The billions of supercharged T cells are produced and then infused back into the patient. The whole process takes about three weeks. “We are entering a new frontier in medical innovation with the ability to reprogram patient cells to attack a deadly cancer,” FDA Commissioner Dr. Scott Gottlieb said in a statement.

According to the Food and Drug Administration, tisagenlecleucel can cause serious side effects, including cytokine release syndrome (CRS), a toxic flood of cytokines that can lead to flu-like symptoms, high fever, and/or life-threatening neurological effects and / or other side effects. . The Food and Drug Administration (FDA) requires that hospitals using the treatment be accredited and trained to recognize and manage CRS. Besides approval of tisagenlecleucel, the FDA has expanded approval for tocilizumab (Actemra® ⁾ for the treatment of CRS and has determined that CAR T-cell therapy should not be given unless tocilizumab is immediately available. Also, since CD19 is present in healthy B cells, tisagenlecleucel can kill these cells as well, increasing the risk of infection.

Revolutionary treatment for leukemia

Emily Whitehead is one of the first CAR T-cell therapy patients who was 6 when she was treated at Children’s Hospital of Philadelphia in a story that appeared on the PBS series. Cancer: the emperor of all diseases . Emily was on the verge of death when she was given a dose of CAR T cells that had been modified by a virus derived from human immunodeficiency virus (HIV). Emily is now 12 years old and shows no signs of active disease. He appeared with his parents at an FDA hearing about the treatment. Emily had ALL, a type of cancer in which the bone marrow makes too many defective lymphocytes.

In many cases, ALL is successfully treated with chemotherapy, stem cell transplantation, or targeted therapy. But in some cases, these treatments do not produce sufficient results and the disease becomes very resistant. In a clinical trial, 52 of 63 patients (82 percent) with relapsed or refractory B cells showed no signs of disease within three months of treatment with tisagenlecleucel. Dozens of clinical trials are underway to determine if CAR T cells could be a treatment option for other blood cancers, including lymphoma and other types of leukemia, as well as cancers with solid tumors, such as brain and maternal cancer. “Additional research efforts will be required to determine the role of this somewhat new approach in cancer management,” says Dr. Markman.

Learn more about hematological oncology, the field of cancer care dedicated to the diagnosis and treatment of blood cancers.