CAR T-Cell Therapy: Re-Engineering the Immune System to Fight Cancer

A young mother, home again with her 3 small children. A teacher back in the classroom for a new school year. A father looking forward to his son’s wedding. All are very different individuals who experienced a similar journey. All faced aggressive, resistant blood cancer and a grim prognosis.

And all achieved stunning remissions following revolutionary CAR T-cell therapy.

The University of Kansas Cancer Center, a National Cancer Institute-designated cancer center, is among the nation’s first cancer centers to provide all of the FDA-approved CAR T-cell treatments. These include YESCARTA™, approved to treat all adults with refractory, aggressive non-Hodgkin lymphoma, and KYMRIAH™, indicated for both patients up to 25 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) and for all adult patients with relapsed or refractory non-Hodgkin lymphoma. These treatments represent the latest advances in precision cancer medicine.

CAR (chimeric antigen receptor) T-cell therapy is advanced cellular therapy that marshals the body's own immune system to lead the fight against cancer. The patient's T cells – integral to the function of the immune system – are extracted from the body, genetically re-engineered in the laboratory to recognize cancer cells, and returned to the body supercharged to seek and destroy cancer.

The therapy represents one of the most exciting developments the field of cancer care has experienced in decades.

A single modified T cell has the ability to attack and kill many thousands of cancer cells. The re-engineered cell is returned to the patient’s bloodstream and sweeps through the body. It attaches to a cancer cell, punches a hole in it and releases a molecule called a granzyme into the cancer cell. That granzyme destroys the cancer cell's DNA. Once the T cell has done its job, it breaks loose from the eradicated cancer cell and moves on to repeat the process. As millions of modified T cells are released into the body, the process is replicated countless times.

We have seen some truly amazing results not previously achieved in the types of patients we are treating. The principal diseases that have been successfully targeted are ALL – the most common childhood and young adult leukemia – and diffuse large-cell lymphoma – the most common form of non-Hodgkin lymphoma in adults. Patients who have qualified for CAR T-cell therapy to date are those with relapsed or chemotherapy-resistant disease. They are patients extremely unlikely to respond to subsequent types of chemotherapy and whose survival is measured in months, not years.

With CAR T-cell therapy, our field has been achieving complete remissions in this patient population – 85% for patients with ALL and 50% for patients with diffuse large cell lymphoma. These results are unprecedented and highly promising.

CAR T-cell therapy is a complex treatment, and it takes a complex, multidisciplinary team to administer it and manage its challenges and side effects. At The University of Kansas Cancer Center, we have that team. It's part of the reason we became one of the world's first providers of CAR T-cell therapies.

Our patients benefit from the experience and expertise of the region's largest blood and marrow transplant and cellular therapeutics program. Our experience from more than 3,700 stem cell transplants benefits every patient receiving CAR T-cell therapy as they receive a transplant of supercharged T cells. We are knowledgeable about and prepared for the complications most common to CAR T-cell treatment. These are:

• Cytokine release syndrome (CRS). High levels of inflammatory cytokines cause intense fever-like symptoms, including tachycardia, hypotension and hypoxia.
• Neurotoxicity. High CAR T-cell levels or cytokine levels can cause confusion, tremor, aphasia, encephalopathy and seizures.

Our nurses, coordinators and navigators focus on the needs of transplant patients every hour of every day. We offer a 24/7 acute leukemia hotline to assist patients in crisis. Further, we collaborate daily with neurointensivists to help prepare for effective neurotoxicity treatment should that complication occur. These are but a few of the many examples of the specialty resources and experience we offer to give our patients fighting blood diseases the best possible chance at the best possible outcome. This experience benefits CAR T-cell therapy patients receiving a promising but new and complicated blood cancer treatment.

While early results are exciting, the future is even more so. Today, blood cancers represent the first FDA-approved indications for CAR T-cell treatment, but hundreds of clinical trials are underway, including at our cancer center, to extend applications. From additional forms of leukemia to multiple myeloma, more blood cancers stand poised to benefit from a CAR T-cell approach. Solid tumors, too, are being studied and targeted with CAR T-cell therapy techniques. Trials in process are exploring the efficacy of CAR T-cell treatment in breast cancer, colon cancer and lung cancer, for example.

In addition to applying cellular therapeutics to additional cancer types, some of these trials are exploring the effect of CAR T-cell therapy earlier in the disease process. While approved therapies are available only for those patients with specific cancer types who have already failed 2 traditional treatments, some immunotherapy clinical trials currently enable patients to receive CAR T-cell therapy after failing a single traditional therapy. The ZUMA-7 trial, of which our cancer center is an enrolling site, is an example.

We envision a future in which CAR T-cell therapy is available sooner and more affordably for more patients as it becomes more efficient and effective.

Dr. McGuirk is the division director of hematologic malignancies and cellular therapeutics at The University of Kansas Cancer Center. His areas of expertise include blood and marrow transplantation, cellular therapeutics, hematological malignancies, hematology and medical oncology.