In addition to the traditional pillars of cancer treatment—surgery, chemotherapy, radiation therapy—a new approach has emerged. This approach is called immunotherapy. One type of immunotherapy that has recently garnered much attention following successful FDA approval is chimeric antigen receptor T-cell (CAR-T) therapy, the first gene therapy in the United States.
What is immunotherapy?
Immunotherapy is a treatment for cancer that uses an individual’s own immune system to fight cancer. It is a type of biological therapy that uses substances from living organisms to treat cancer. Different kinds of immunotherapy include the use of monoclonal antibodies, cytokines, treatment vaccines, as well as adoptive cell transfer. This final category of cell-based immunotherapies, which includes CAR-T therapy, is emerging as a promising new treatment for cancers.
How does it work?
CAR-T therapy uses apheresis, a method of removing whole blood from a patient. The collected blood is centrifuged in order to separate the components of the blood; those that are not needed are re-infused into the patient. In CAR-T therapy, T-cells (a type of white blood cell or immune cell) are separated from the whole blood and then genetically engineered to express a chimeric antigen receptor on the cell membrane. The chimeric antigen receptor (CAR) has an external target-binding domain designed to recognize a tumor antigen (a molecule that induces an immune response that is produced in tumor cells) and an activation domain that is responsible for activating the T-cell when the CAR-T binds to the target cell (the tumor cell). These CAR-T cells are finally infused back into the patient.
Results so far:
In terms of clinical development, Novartis is leading the pack. It is the designer of the CTL019 therapy (also known as Kymriah), which the FDA collectively voted in favor of. Results from the Novartis Phase II clinical trial in B-cell acute (sudden or temporary) lymphoblastic leukemia (ALL) achieved full remission—in other words, the cancer was gone—within 3 months in 82% of patients. However, 50% of patients did suffer from some serious and potentially deadly side effects, such as cytokine-release syndrome (CRS), which can cause high fever, low blood pressure, and issues with oxygenation of the lung.
What’s next?
CAR-T therapy has been primarily limited to small clinical trials, principally in patients suffering from blood cancers. In its approval of Kymriah, the FDA concluded that the therapy’s benefits for ill children outweigh any possibly risky side effects. The FDA vote came after drawn-out discussion with the fathers of two young patients whose lives were saved by the therapy. Novartis’ CAR-T therapy became the first therapy based on gene transfer approved by the FDA. Not only has one therapy been approved, the FDA has forged ahead and recently approved a second CAR-T gene therapy, Yescarta, by Kite Pharmaceuticals, for certain types of non-Hodgkins lymphoma (NHL).
While CAR-T therapy may be worth the risk, there is still a long way to go, such as developing new and improved versions of the therapy and expanding the therapies out to a wide range of patients. Nonetheless, progress is being rapidly made as CAR-T holds the promise for a new highly effective approach to treat cancer patients. The recent FDA approvals reveal the momentum for this encouraging new area of therapeutic medicine; in coming years, we should expect many other pharmaceutical companies to be following suit. Who will be the next?
