CAR-T therapy: Genetically-engineered cells that fight blood cancer
June 29, 2018
When common blood cancer treatments fail, immunotherapy called chimeric antigen receptor T-cell therapy (most commonly known as CAR-T therapy) gives patients another option: genetic engineering of their own immune systems to kill cancer cells.
CAR-T therapy is designed to attack a patient’s unique cancer cells. It is the pinnacle of personalized treatment and requires a variety of medical experts.
The treatment is highly effective and, perhaps, can provide a framework for discovering future cures for cancer. Because this therapy is relatively new, there is still much to improve and much to learn about the ideal time in a patient’s journey to introduce CAR-T. Today, candidates for CAR-T therapy are patients for whom other therapies have failed to cause remission.
How does CAR-T work?
In a patient who has been diagnosed with cancer, the T-cells that typically fight against infections (and should also fight the cancer) have decreased in number or are nonfunctional. For CAR-T therapy, the doctor draws the patient’s blood through a process called leukopheresis, collecting a relatively small number of T-cells. Specialists modify the cells with the chimeric antigen receptor, a specially created receptor that is designed to bind to specific proteins on cancer cells. This reprograms the T-cells to recognize and attack the patient’s specific cancer.
The engineered T-cells, now stronger and “smarter,” are cultured in the lab to reach exponential numbers and then infused into the patient. Because these cells are specific to each individual patient’s cancer, the treatment cannot be produced in advance – there is no “one-size-fits-all” CAR-T therapy. In order to create the most effective therapy, we carefully grow T-cells in the lab, which sometimes can take several weeks. During this time, patients often receive “bridging therapy” to keep their cancer at bay.
One of the many attractive features of CAR-T therapy is how the T-cells are manufactured. Most of the time, patients need only a one-time infusion of CAR-T cells. While it is common for patients who receive other types of therapy to require maintenance treatment, CAR-T patients do not need maintenance therapy to keep their cancer under control. Due to the unique “stimulatory switch” on these CAR-T cells, they can circulate in the blood for a long time, continuing to kill cancer cells.
The entire treatment process – from being evaluated for CAR-T therapy to finishing the infusion – can take 12 to 16 weeks. Patients receive CAR-T cell infusion in the hospital; individual reactions vary, and, some patients might need prolonged hospitalization if severe side effects occur. Patients commonly are required to stay close to the hospital after discharge for frequent checks and monitoring.
Does CAR-T therapy cause side effects?
The newly strengthened T-cells can attack not just the cancer but sometimes other parts of the body, causing cytokine release syndrome – an umbrella term for a set of potential side effects from CAR-T or other immunotherapy. The syndrome, which occurs in approximately a quarter of CAR-T patients, includes symptoms that can be as mild as a headache and nausea or, in some cases, severe enough to require prolonged hospital stay and perhaps the use of a breathing machine or other life-sustaining measures. In rare cases, patients can have seizures caused by brain inflammation.
Controlling these side effects requires a variety of medical experts who can monitor patients closely until symptoms subside. It is critical that patients receive CAR-T therapy at a facility that offers care from a team experienced with the treatment and have access to the most up-to-date knowledge, training, and education involving CAR-T therapy – every nurse, technician, and doctor must be ready to respond to complications at a moment’s notice.
Despite the potential for complications, most of my patients would say the possibility that CAR-T might extend their life far outweighs the side effects they might experience. We use this therapy to treat patients with blood cancers only when we’ve not had success with other treatment methods, so although patients might be taking a risk, CAR-T could be the treatment that gives them many more years with their loved ones.
What drugs are approved, and for which cancers?
The Food and Drug Administration (FDA) has approved two CAR-T therapies: KYMRIAH® can be used to treat leukemia and lymphoma, and YESCARTA® can be used to treat lymphoma. Though the FDA has not approved any CAR-T therapies in myeloma patients, UT Southwestern experts are researching specific therapies in hopes of obtaining an approval to make treatment more readily available outside of clinical trials. In fact, we are one of just nine hospitals in the United States participating in one of the most advanced phases of CAR-T therapy clinical trials for multiple myeloma.
I see myeloma patients who have undergone 7,8,9 types of chemotherapies, and nothing has worked. Through our clinical trial, CAR-T therapy has given patients the chance at longer, healthier lives, and it is amazing to be involved in that process.
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