‘Triple Threat’ clinical trial and efforts to expand CAR-T therapies advance cellular cancer treatments

Researchers from The University of Kansas Cancer Center gave an update on the latest breakthroughs and challenges for a type of cellular cancer treatment known as CAR-T therapy in the Oct. 8 episode of Open Mics with Dr. Stites. This show, produced by The University of Kansas Health System, is one of many streaming on their channels that also are broadcast into media newsrooms and available as podcasts.

“Open Mics” is hosted by Steven Stites, M.D., executive vice chancellor of the University of Kansas Medical Center and chief medical officer for the health system.

CAR-T (chimeric antigen receptor T-cell) treatment is a form of immunotherapy, meaning it uses the body's immune system to recognize and destroy cancer cells. Seven different CAR-T therapies have been approved by the U.S. Food and Drug Administration (FDA) since 2017, and even more are still investigational, such as the one being tested in the "Triple Threat" clinical trial.

CAR-T therapies have had great success treating certain blood cancers, including leukemia, lymphoma and myeloma. But significant challenges remain, including expanding access to rural patients and improving the effectiveness of these therapies. Stites noted that researchers and physicians at KU Cancer Center are working on both these issues.

“I want you to know that CAR-T cellular therapy has profoundly changed the way we treat some cancers, yet many patients who would benefit from these treatments don't have access,” Stites said. “The American Society of Transplantation and Cellular Therapy recently published a study detailing a national crisis happening with access to CAR-T. Only a small fraction of patients is receiving this curative therapy.”

Stites’ guests on the show were Joseph McGuirk, D.O., director of the Division of Hematologic Malignancies and Cellular Therapeutics at KU Cancer Center, and Al-Ola Abdallah, M.D., associate professor of hematologic malignancies and cellular therapeutics at KU Cancer Center and director of Plasma Cell Disorders Care at the health system.

McGuirk explained the science behind CAR-T therapies. “This is based on decades of research in how the body’s immune system controls, not just infection — the immune system has another important job, and that is looking around the body for any cells that are misbehaving and have the potential to turn into cancers. It can head them off at the pass and attack them.”

Stites asked if this ability to “teach” the immune system is the great takeaway for future research studies and breakthroughs.

“Maybe they could recognize some other types of disease, some other things that shouldn’t be happening with these cells and take care of it. It’s like Steve Spagnuolo teaching the defense to recognize what the offense is trying to do,” Stites said, referring to the Kansas City Chiefs’ defensive coordinator.

Stites noted that while these therapies have tremendous research potential and have been revolutionary in certain types of cancer where they are already FDA-approved, the general public might not realize that many types of CAR-T therapy are now considered standard treatments, covered by insurance.

Abdallah and McGuirk agreed, noting that more educational efforts are needed to help patients understand that cellular therapies might be an option for them.

KU Cancer Center researchers are looking at ways to expand access to the therapy, perhaps by making it cheaper to produce those cancer-fighting cells with the use of an “off-the-shelf” version of the T cells.

McGuirk also pointed out that KU Cancer Center research has shown that access is a concern. “The further you live from a comprehensive cancer center like ours, the lesser the chance that you are going to know about and have access to clinical trials and to complex therapies that are standard-of-care, likes CAR-T therapy,” he said.

Stites also referenced the clinical trial participant in the video, Michael Fong, who enrolled in the Triple Threat trial after experiencing a relapse of his cancer. “His cancer came back. Why is that?” Stites asked.

McGuirk explained that cancer cells can mutate and change. Triple Threat therapy helps circumvent that problem by programming the T cells to attack three molecular targets, rather than just one.

While Triple Threat is still at the investigational stage, McGuirk noted that the progress of trial participants like Fong is a reason for hope.

“I can’t share specifics,” McGuirk said, noting that it is an ongoing, first-in-human clinical trial. “But I can tell you that we are encouraged.”

“We hope that this (Triple Threat) is the future. We are getting smarter and smarter,” McGuirk said. “Things like Triple Threat — new strategies to target these cancer cells — are going to keep moving that ball down the field for our patients.”