A clinical research staff member pushes a cart through a light-filled hallway, carrying a patient’s CAR T cells and supplies for their infusion

How future cures begin as ideas in laboratories

The successes of CAR T research show the importance of the cycle of science—sparking new ideas and clinical trials that give patients better options.

  • Nicole Sweeney Etter and Rachel Ewing
  • July 10, 2025

Jane Gesemyer, a former realtor from Newtown, PA, was 67 when she got an explanation for her sudden debilitating exhaustion: mantle cell lymphoma. She started chemotherapy, but her cancer resisted treatment. Her doctor then referred her to the Abramson Cancer Center at Penn Medicine for CAR T cell therapya treatment option approved by the Food and Drug Administration (FDA) for several forms of leukemia, lymphoma, and myelomaand first made possible thanks to two decades of research at Penn.

The story behind Gesemyer’s treatment exemplifies the virtuous cycle of research—from idea to laboratory science, private industry investment, and back to new cycles of discovery.

From unpopular idea to the frontier of future discovery 

Jakub Svoboda, MD, holds a stethoscope to the heart of Jane Gesemyer, a woman in her 70s, who is smiling
Jane Gesemyer with oncologist Jakub Svoboda, MD

There was a time in the late 1990s and early 2000s when the idea of CAR T cell therapy was outside the medical mainstream. But Carl June, MD, Bruce Levine, PhD, David Porter, MD, and an enthusiastic set of colleagues at Penn and Children’s Hospital of Philadelphia persisted, convinced that CAR T had enormous potential. Philanthropic support—especially funds from Leonard and the late Madlyn Abramson’s gift to launch the Abramson Family Cancer Research Institute—helped them start their first human trials. Eventually, their years of hard work, and a partnership with a major pharmaceutical company to advance and test their discoveries, resulted in the first CAR T therapy to receive FDA approval in 2017

The first successes of CAR T opened the floodgates to more research that could harness the power of the body’s own immune cells to fight cancer. Federal research grants funded more studies, and promising academic discoveries led to startup companies that licensed and would develop the technology into new therapies. Philadelphia’s growing reputation as a global hub for new cell therapies soon earned it a new nickname: “Cellicon Valley.” Researchers were eager to expand this transformational technology in an attempt to also defeat solid tumors, more treatment-resistant blood cancers, and even other conditions, like autoimmune disease and heart disease. 

Among the numerous new CAR T cell approaches studied in labs on Penn’s campus: 

  • A few teams are exploring ways to create CAR T cells in vivo—meaning the cells are engineered within the body, without the need to extract T cells and modify them in a lab. The approach may have the potential to revolutionize the power of CAR T cells—saving time, money, and making these personalized therapies more accessible to patients.
  • Donald M. O’Rourke, MD, the John Templeton, Jr., MD Professor in Neurosurgery and director of the Glioblastoma Translational Center of Excellence in the Abramson Cancer Center, created a novel dual-target approach that directs CAR T cells to two proteins commonly found in brain tumors. 
  • June, the Richard W. Vague Professor in Immunotherapy and the director of the Center for Cellular Immunotherapies, led a team that developed a next-generation armored CAR T cell treatment. These engineered T cells not only attack the cancer, but also secrete engineered immune factors to enhance the killing. 

The way Penn teams have taken on CAR T discovery and development opportunities is emblematic of how research ideas proliferate in other domains: The spark of an idea of how a particular cell or molecule could be harnessed to stop a tumor or spur healing, leads to carefully designed laboratory studies to find evidence for those ideas which have true potential for impact and warrant further development.

Creative ideas born in labs often depend on federal funding to light the flame of that spark. In fact, for the last 20 years, more than half of National Institutes of Health (NIH) funding has been awarded for basic, rather than applied research. NIH funding contributed to the development of more than 99 percent of new drugs that received FDA approval from 2010-2019, with more than 80 percent of these NIH funds devoted to basic research on the drugs’ targets. 

New clinical trials, new possibilities for patients 

Early investments are crucial to getting the most promising research ideas from the laboratory to the patient’s bedside for further evaluation. In 2023, Stephen Bagley, MD, MSCE, an assistant professor of Hematology-Oncology and Neurosurgery at Penn, administered dual-target CAR T cells to the initial patient in a first-in-human clinical trial for glioblastoma. The trial was made possible by partners like Kite, a Gilead company (which previously acquired a Penn-based startup), and Rosanna and John Gabriele Troiano, a Wharton alumnus.

Stephen Bagley, MD, injecting CAR T cells into a male patient in a hospital bed while clinical research staff stand nearby observing and taking notes
Stephen Bagley, MD, injects CAR T cells into a patient participating in the dual-target CAR T clinical trial in November 2024.

The next day, a text message flashed up on Bagley’s phone: The patient’s MRI results were in.

“I saw that the tumor had essentially disappeared, and I was shocked,” he recalled. “This could have been a complete dud, like the other thousand things that have been studied for glioblastoma over the decades. So to see that first tumor shrink was definitely a great moment.”

Nearly two-thirds of patients in the trial experienced tumor reduction, including Eduart Cuka, a 55-year-old father of two who recently attended his younger child’s college graduation in good health and good spirits, nearly a year after his first CAR T infusion in the trial. While the tumors eventually regrew for most patients in the trial, one patient’s cancer has remained stable for more than 16 months after a single dose of the dual-target CAR T cells. There is more work to be done, but extending survival time for patients with glioblastoma is a significant accomplishment—and it provides important clues to advance the work even further.

“The fact that we’re on the right track gives all of us doing this work more hope,” noted Bagley, who recently published his results in Nature Medicine. “I think it’s only a matter of time until the puzzle is solved.”

Nicolas Sarmiento pointing to MRI brain scan results for Eduart Cuka, who looks on
Eduart Cuka learned in June 2025 that his glioblastoma tumor had shrunk again after his second infusion of CAR T cells.

Still, there are many more puzzles, and many more trials.

Jakub Svoboda, MD, an associate professor of Hematology-Oncology, recently led a clinical trial for treatment-resistant lymphoma using an “armored” CAR T cell therapy based on June’s research. Among the trial’s participants was Gesemyer, whose cancer had returned nine months after her first CAR T treatment. The new CAR T product reduced cancer for more than 80 percent of the trial’s patients and led to remission for more than half of participants—including Gesemyer.

“We couldn’t do any of this without the patients,” said Svoboda, who recently published his results in the New England Journal of Medicine. “Patients deserve a lot of credit for the success of these trials, for their willingness to try new things and for trusting us.”

Gesemyer was grateful for the opportunity to participate in a clinical trial—and to get back to playing with her two grandsons. “It saved my life,” she said. “That research is super important. Even if it hadn’t worked for me, I would still be glad that I did it.”

Jane Gesemyer holds hands with her two grandsons
Jane Gesemyer with her two grandsons after completing her cancer treatment 

The cycle continues 

But clinical research is expensive. Bagley’s glioblastoma trial was partially funded by Kite, a Gilead Company, which previously acquired Tmunity Therapeutics, a startup company formed by Penn researchers in 2015 to advance academic discoveries in cellular therapies toward the clinic. Kite will also fund the next phase of Svoboda’s “armored” CAR T trial, after the initial trial was funded by the University.

Partnerships with industry make it possible for therapies to be studied in greater numbers of patients, a critical step to eventually secure approval from the FDA.

“I think together we can accomplish things much better and faster than if either of us tried to go it alone,” Bagley said.

The Penn Medicine Co-Investment Program provides an important framework for Penn to partner with startup companies—and drive impact on both the economy and job creation, and on the testing of future treatments at a larger scale.

“From the inception of an idea to an FDA-approved therapy, you’re talking minimum of a decade. To keep that timeframe as fast as possible for patients and to move these advances into a place where they can actually benefit people, this virtuous cycle becomes incredibly important.”

Stephen Bagley, MD, MSCE

And there is always more work to be done to help the patients that don’t respond to a new treatment. That means returning to the lab and turning new cycles of the discovery process, which takes more time and funding.

And so each research question spurs new directions, questions, and ideas:

In the dual-target CAR T trial for glioblastoma, Bagley’s team is now exploring the efficacy of a second CAR T infusion two weeks after the first. Researchers are also testing the approach with newly diagnosed glioblastoma patients, whose cancer might be even more responsive than those who have already undergone multiple other types of treatment. Back in the lab, researchers are further engineering CAR T cells in hopes of making them more effective against glioblastoma.

Eduart Cuka and Stephen Bagley, MD, smile and shake hands while seated in an infusion room
Bagley’s team continues to explore ways to improve the dual target CAR T cell therapy for glioblastoma to build upon what they have learned through the trial that enrolled Eduart Cuka. 

Researchers will also refine the “armored” CAR T cell treatment and are conducting trials with other blood cancers, such as chronic lymphocytic leukemia and acute lymphoblastic leukemia. Svoboda hopes to eventually test the treatment with solid tumors as well. “I think there’s a lot of hope that this treatment could really improve the outcomes in solid cancers,” he said.

And elsewhere at Penn, researchers continue to push forward research on a host of other diseases.

It’s especially vital for academic researchers to drive new cycles of discovery because it’s rare for the private sector to prioritize early-stage science, amid demands from investors for shorter-term profits.

“From the inception of an idea to an FDA-approved therapy, you’re talking minimum of a decade,” Bagley said. “To keep that timeframe as fast as possible for patients and to move these advances into a place where they can actually benefit people, this virtuous cycle becomes incredibly important.”

It takes a whole ecosystem of dedicated people willing to invest time, energy, creativity, and resources to create the next set of possible breakthrough treatments. But for the patients who volunteer for trials and those who eventually benefit from new treatments, the payoff is priceless.

“It is not like we had many options to choose from, but we definitely had the option to fight,” Eduart Cuka said, calling the choice to join a trial “the best decision of my life.”

Read more about the cycle of research discovery 

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