A Revolution In Cancer Therapy

Joseph McGuirk, DO, and Mary Kate Funk, RN, BSN

Immunotherapy, a relatively new concept in cancer treatment, has picked up steam over the last three or so decades. In 1985, Steven Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute (NCI), pioneered the development of immunotherapy by removing a patient’s white blood cells, modifying them in the lab and infusing the cancer-fighting cells back into the patient. Since then, researchers have continued to look for ways to harness the immune system for the treatment of cancer.

More recently, the field made an unparalleled surge forward with the emergence of a novel treatment concept called CAR (Chimeric Antigen Receptor) T-cell therapy. CAR T-cells are engineered immune cells specially trained to identify and fight cancer. In 2017 and 2018, the U.S. Food and Drug Administration (FDA) approved the use of such therapies in two types of blood cancers.

According to Joseph McGuirk, DO, division director of the hematologic malignancies and cellular therapeutics program at The University of Kansas Cancer Center, the advances validate immunotherapy’s place among cancer care’s original four pillars, which are chemotherapy, radiation, surgery and targeted therapy.

“We are in a remarkable and truly revolutionary time for cancer therapeutics,” McGuirk says. “Immunotherapy has made significant advances. Experts believe it has become a ‘fifth pillar’ among the other tried-and-true therapies.”

Arming the T-cells

White blood cells are required for good health and protection against disease. They flow through the bloodstream, finding and attacking foreign invaders like bacteria and viruses. To help the cells identify elusive cancer cells, CAR T-cell therapy involves taking T-cells from a patient, genetically modifying them with an artificial receptor that targets cancer cells and reinjecting them back into the patient. Once infused, they multiply and attack tumor cells.

Two CAR T-cell drugs have been approved by the FDA so far. YESCARTA™ is available to some adult patients with aggressive non-Hodgkin lymphoma that has relapsed after prior treatments or has not responded to other therapies. KU Cancer Center played an important role in the approval of the second drug, KYMRIAH™.

The only National Cancer Institute (NCI)-designated center in the region, KU Cancer Center was the first of 27 sites around the world to enroll patients in the multi-national Phase 2 study, called the JULIET trial. KU Cancer Center treated more patients in the study than any other participating site. KYMRIAH is approved for patients up to 25 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) and for adult patients with relapsed or refractory non-Hodgkin lymphoma.

The results, McGuirk says, are stunning. About 50 percent of KYMRIAH study participants with non-Hodgkin lymphoma achieved complete remission, and 85 percent of patients with ALL achieved 85 percent remission.

The outlook is usually grim for patients who have relapsed and are chemo-resistant. Survival is expected to be quite short, numbered in months, not years,” McGuirk says. “The results are unprecedented.

McGuirk adds that the majority of those who achieved complete remission are maintaining that remission with longer term follow-up.

Shaping Future Treatments

Currently, KU Cancer Center is the only institution in Kansas to offer all available forms of CAR T therapy.

Administering CAR T-cell therapy is a complex endeavor, and providers are working to make these scientific advances more readily available to qualified patients. Closing the gap is of utmost importance, McGuirk says, but best practices must first be established.

“We are home to the largest and most experienced blood and marrow transplant and cellular therapeutics program in the region,” McGuirk explains. “You must have the expertise, accreditation and infrastructure to give this complex therapy safely and effectively.”

Learn more about CAR T-cell therapies available at KU Cancer Center.

McGuirk and his team published a study to help centers set up the infrastructure to offer CAR T-cell therapy. In 2018, McGuirk was elected to lead a national initiative to advance the use of CAR T-cell therapies. Established by the Association of American Cancer Institutes (AACI), the goal is to develop and disseminate best practices for centers offering the therapy.

While blood cancers have been the catalyst for these advances, researchers and physicians hold the same hope for CAR T-cell therapy success in solid tumors. KU Cancer Center researchers in the lab are applying immunotherapy and CAR T-cell therapy concepts to the stomach, brain and other parts of the body. In the clinic, multiple cellular therapy-based trials are open for enrollment with several more in start-up.

“The fields of cancer research and care are on an incredible trajectory. It’s a remarkable time to be a doctor, nurse or researcher,” McGuirk says. “When we look back, I think we are going to see it as a turning point, when the very landscape of cancer medicine changed.”




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