By: Nicole Sweeney Etter
From left, research coordinator Nicolas Sarmiento, project manager Reenie Martins, research coordinator Lee Dengel, and trial sample coordinator Rutendo Manyeka document and prepare paperwork required for T-cell infusion.
For more than a decade, Penn Medicine clinical research nurse Joanne Shea, MS, BSN, RN, has had a front-row seat to the groundbreaking research underway in the Center for Cellular Immunotherapies. As Abramson Cancer Center patients volunteer to participate in clinical trials of investigational treatments, often at a time when they have an incurable cancer that is resistant to conventional treatments, Shea does her part to advance the science.
Shea had always been intrigued by research, and she was hooked after working on one of the earliest trailblazing studies of CAR (chimeric antigen receptor) T cell therapy to treat lymphoma patients. That research at Penn Medicine ultimately paved the way for this therapy’s second approval from the U.S. Food and Drug Administration (FDA), in 2018. The treatment extracts a patient’s own immune cells, genetically modifies them in a specialized lab, and then reinfuses the engineered cells into the patient to target and destroy cancer cells. Building on this success treating blood cancers, Shea is part of the team at Penn Medicine that is now expanding into CAR T cell therapy for hard-to-treat solid tumors, including glioblastoma, an aggressive form of brain cancer.
“It’s totally different from bedside nursing, and I just find it fascinating,” said Shea, whose job involves administering these novel treatments to patients, assessing them in follow-up visits, collecting and entering data, and more. “We’re dealing with cutting-edge technology here, and it’s exciting when you see that something is working. We’ve treated patients who were extremely sick and without other options, and to be able to witness their return to normal life cancer-free is amazing. I love having it happen right in front of my eyes.”
Bringing innovation to the bedside
As Dr. Steven Bagley administers CAR T treatment cells, research coordinator Lee Dengel prepares tubes for the collection of research samples.
Throughout Penn Medicine and the Abramson Cancer Center, dozens of on-the-ground clinical trial support staff help execute the team science that brings research discoveries from the lab bench to the bedside. In the case of CAR T cell therapies that were pioneered at Penn and continue to be ripe areas for innovation, renowned scientists including Center for Clinical Immunotherapies (CCI) Director Carl June, MD, the Richard W. Vague Professor in the Department of Pathology and Laboratory Medicine, Bruce Levine, PhD, the Barbara and Edward Netter Professor in Cancer Gene Therapy, and David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence, lead the research vision. To achieve that vision, the quiet work of staff members behind the scenes is vital to moving the science forward.
The CCI’s Clinical Trials Unit recently received Penn Medicine’s Innovations in Clinical Research Operations Award, which recognizes “groups or individuals who build systems that improve how we conduct clinical research at Penn Medicine.”
“I really have to give resounding kudos to our team of research nurses and research coordinators because coordinating CAR T cell therapy is very complex,” said Lester Lledo, DNP, RN, CRNP, the unit’s director. “The patients are very complicated, they’re very sick, a lot of them have late-stage disease, and they’re being treated in a trial that’s also very complex. On top of that, our staff also need to be very creative and innovative because we are often traveling in uncharted territory with these first-in-human trials.”
That experience has a ripple effect at Penn Medicine and beyond. In the award nomination form, June referred to the team as “go-to veterans in research nursing, coordination, and consulting for other groups venturing into their first CAR T cell therapy trials.” These staff have mentored other study nurses and research coordinators on everything from how to administer CAR T cell infusions at the bedside to how to manage the logistics and nuances of CAR T cell studies. The team has touched areas representing cell therapy trials in many other areas, from the Neurosurgery Department to the Prostate and Kidney Cancer Program to the Cell Therapy Transplant Program in the Division of Hematology and Oncology.
Inventing new ways to work
The CCI Clinical Trial Unit’s team is small—about 20 people—but experienced thanks to high employee retention rates. Some of the staff have been on board since Penn Medicine’s inaugural CAR T cell therapy trial in 2010 and have since watched the team grow and take on increasingly sophisticated trials.
“What’s very rewarding is that it never stays stagnant here,” said Karen Dengel, RN, BSN, the unit’s research nurse manager. “We’re always pushing the envelope to figure out new ways to treat cancers.”
One of the questions the team needs to ask again and again: “How do we do this?” With each clinical trial and treatment population, they need to develop novel workflows and delivery methods for CAR T cell therapy, whether they are infusing the treatment directly into a body cavity, artery, tumor or the space between the spinal cord and its membranes. Sometimes they have to take equipment designed for one need and adapt it for CAR T cell therapy.
Detailed study protocol documents direct every step, “but we have to do the hands-on work to figure out how to make it reality at the bedside,” said Joan Gilmore, CCRP, the unit’s associate director.
The latest challenge has been shifting from IV infusions for blood cancers to more targeted treatments for solid tumors. For the current glioblastoma trial, the FDA required CAR T cells to be delivered locally into the brain, so the team adapted techniques used for chemotherapy that is delivered into the fluid around the brain and spinal cord. The team uses a quarter-sized device implanted under the scalp—to direct the CAR T cells into the relevant area.
What happens after treatment delivery is just as important. Data collection is essential to monitor patients’ response to the treatment, and study protocols can be modified as clinical research staff learn more information.
“Our trials are very complex, and the product that’s given to the patients can cause some severe, serious adverse events,” Dengel said. “So there’s a lot of information that needs to be gathered for safety, and that’s critical because we need to make sure the treatments are safe for other patients.”
Throughout all the intricacies of conducting clinical trials, the team never forgets the humans at the heart of their work. “Patients come first—that comes before data,” Shea said.
Commitment to the mission
The work requires commitment from patients as well. CAR T cell therapy involves intensive procedures and monthly monitoring, on top of the physical and emotional demands of life with cancer. Patients come from around the world to access many of Penn Medicine’s clinical trials, often after exhausting other treatments. They commit to participating knowing that the study might not deliver a Hail Mary moment for themselves but might help advance better treatments and cures for future patients.
“Participating in a clinical trial when you’re dealing with a serious illness can be overwhelming and scary, but there are people that are here to help you navigate through that,” Gilmore said.
One of them is clinical project manager Reenie Martins. She previously worked as a veterinary clinical research nurse at Penn Vet, where she cared for animals undergoing treatment for cancer, heart disease, and other medical issues. Then five years ago, she decided to transition to the human side of clinical research.
As a research coordinator on the glioblastoma trial, Martins spends her days scheduling patients’ appointments, visiting with patients, entering data, and writing reports of adverse events. She loves the complex project management it requires, along with the patient relationships.
“We have to ask so many questions of patients enrolled in studies,” Martins said. “I always give them a heads up in the beginning: ‘If you haven’t been on a trial before, get ready for a lot of questions because we are the nosiest people in the world.’ So we get to know patients really well. And I think it comforts patients and families to know that they have this one point person who shepherds them through this complicated process.”
While getting to know patients over many months or even years is one of the joys of the job, working with patients who have terminal cancer can also take an emotional toll— especially when a patient passes away. But the mission to find better cures drives the team forward.
“We believe in the mission that Carl June has instilled,” Gilmore said. “This is an opportunity to be a part of something that’s unique, that’s bringing new therapies to sick patients and to give hope to people out there. That’s what motivates us.”