KU Cancer Center Discovers New Strategies to Treat Blood Cancers
Research pilot projects, supported by One Day. One KU., help identify ways to attack cancer at cellular level
When blood cancers return after standard treatments, the survival rate drops dramatically — to as low as 5%. However, a new therapy is improving those outcomes by combating the cancer at the cellular level. The method has improved success by an average of 50%, and researchers say these promising results are just the beginning.
The new therapy, called chimeric antigen receptor (CAR) T-cell therapy, amplifies the immune system’s ability to recognize and kill cancer cells. The University of Kansas Cancer Center, the only National Cancer Institute (NCI)-designated Comprehensive Cancer Center in the region, played a crucial role in the pivotal clinical trials that paved the way for the approval of these groundbreaking therapies. Funding for research initiatives like this is supported in part by donations from the university’s annual One Day. One KU. giving day. After seeing success treating blood cancers, researchers are now hoping to improve the therapy to be more effective and expand its use to additional cancers in its urgent journey to break the devasting grip of cancer.
“CAR T-cell therapy is a remarkable development in immunotherapy that leverages our better understanding of how the immune system works to fight not just infection but to control the development of cancers in the first place,” said Dr. Joseph McGuirk, division director of KU Cancer Center’s Hematologic Malignancies and Cellular Therapeutics (HMCT) program. “And part of that equation includes not just the cancer cell itself, but its ability to manipulate the immune system around it and shield itself from being recognized as a bad actor, attacked and destroyed.”
KU Cancer Center was the first of 27 sites around the world to enroll patients in a multinational Phase 2 trial for the therapy. The findings led to the first-ever CAR T-cell therapy to be approved by the Food and Drug Administration (FDA). KU Cancer Center also treated more patients in the study
KU Cancer Centerthan any other participating site. As part of the treatment, T-cells are removed from a patient, equipped with new proteins that allow them to detect cancer and infused back into the patient. The new proteins – CARs – recognize and attack specific antigens on the surface of cancer cells. Today, there are six FDA-approved CAR-based therapies to treat certain types of leukemia, lymphoma and multiple myeloma, all of which are available at KU Cancer Center.
KU Cancer Center also hopes to provide a new outpatient clinical space for the Hematologic Malignancies and Cellular Therapeutics division. It is part of a larger vision to build a new world-class destination cancer center that will enhance basic, translational and clinical research efforts by stimulating collaboration and new approaches to benefit patient outcomes. With more than 800 CAR T-cell clinical trials underway, the inclusion of a cellular therapy Good Manufacturing Practice (GMP) facility would be an essential part of the new center. It would enable KU Cancer Center to take advantage of clinical advancements and position the institution to get these new treatments to the patients who need them.
Making A Difference Together
For McGuirk, a national leader in cellular therapy research and treatment, the passion for exploring innovative solutions such as CAR T-cell therapy goes back to an experience he had as a child. When riding with his father, their vehicle collided with a car driven by a drunk driver. Two toddlers in the backseat of the other car, neither wearing seatbelts, were thrown from the vehicle. His father and cousin rushed to the aid of the toddlers, one of whom ended up surviving while the other did not. The experience marked McGuirk, inspiring a career that he describes as a calling.
I realized at that time that you can face terrible, devastating situations like that — like acute leukemia, metastatic cancer — and you can either watch from the sidelines, or you can say, ‘OK, there's a horrible situation. What can we do about it?
~ Dr. Joseph McGuirk, division director of KU Cancer Center’s Hematologic Malignancies and Cellular Therapeutics (HMCT) program
Today McGuirk is spearheading a collaborative effort that will test a new CAR therapy created at the cancer center for the treatment of lymphoma and acute lymphoblastic leukemia. The six CAR T-cell therapies currently approved by the FDA target a single antigen on cancer cells, but in 30% to 50% of people, the cancer stops making the targeted antigen to escape detection. The new therapy would target three different types of antigens, helping eliminate this evasion and increase the success rate.
The collaboration includes researchers at KU Cancer Center, Children’s Mercy and the National Cancer Institute (NCI). McGuirk is working on the effort with Sunil Abhyankar, M.D., a KU Medical Center professor in the Department of Internal Medicine, Division of Hematologic Malignancies and Cellular Therapeutics. McGuirk envisions a future where CAR therapies are given as a first option, instead of after standard treatments have failed.
“If it works in the worst-case scenario, why should we allow patients to wait until the worst-case scenario?” McGuirk said. “Perhaps we should challenge the current standard of care for those patients, which isn't great shakes in terms of outcomes.”
The hope is that CAR therapies can also be used to treat more types of cancers. KU Cancer Center Vice Chancellor and Director Dr. Roy Jensen said while a large part of the focus is improving the therapies’ efficacy and applicability to leukemias and lymphomas, there is no reason the technology couldn’t be translated to more common types of cancers such as breast, lung, colon and prostate.
“It is an engineering question — we just have to find the right targets on those types of tumors,” Jensen said. “Fundamentally, there's no reason why we cannot use CAR T technology to go after these more common epithelial tumors.”
New Pilot Projects, New Hope
CAR T-cell therapy is not the only innovation being researched at the cancer center that is raising hopes for patients and paving the way for future breakthroughs. Jensen said being able to pilot research projects — and having the funds from sources such as One Day. One KU. to support them — has a direct impact on prospects for advancement. He said successfully funded pilot projects often turn into funded grant proposals from the National Institutes of Health and other agencies.
“We've had a great return on investment by doing that because the pilot awards allow investigators to collect preliminary data confirming the validity of their idea,” Jensen said. “It’s very important to be able to show the funding agency that it's not just some idea on a chalkboard. We have some evidence that this might work.”
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