As a thought leader in the world of cancer, the Abramson Cancer Center has been building on its creativity and groundbreaking work in immunotherapy—today’s most rapidly advancing area of medicine—by pushing the boundaries of science to find life-changing treatments for countless patients with cancer and other diseases.
Robert Vonderheide, MD, DPhil, Director of the Abramson Cancer Center, is excited at the prospect and promise of Immune Health® for medicine. At the forefront of these advancements is the Abramson Cancer Center, where dedicated teams are committed to understanding the full scope of its potential.
Penn is home to one of the largest groups of immunologists at any single institution and they continue to push the limits of innovation by building a hub for Immune Health—performing, curating and analyzing patient immune assays to drive new discoveries and shift the paradigms of clinical care.
This starts with integrated data analysis of patient samples, followed by translating that data into clinically actionable immune health information. For example, when COVID-19 first hit, Immune Health was able to deliver results to clinical care teams in real time, ultimately playing a large role in the discovery of new diagnostics and therapies.
The immune system is medicine’s next great frontier. It senses all tissues in the body. It is the voice that tells us about health and disease, and Immune Health is designed to listen. Just as we can monitor intricate details of the heart via an echocardiogram, an Immune Health profile carries great promise for better understanding and treating disease.
Distinct immune signatures are likely found in cancer, infection, autoimmunity, recovery from surgery, preeclampsia, obesity, sleep deprivation, cardiovascular disease, aging and more. A recent Penn Medicine study of immune responses in severely ill COVID-19 patients brought forth important discoveries in COVID care and vaccine strategy, propelling new research in Immune Health. And within the larger ecosystem of the University of Pennsylvania, immunology experts across Penn’s 12 esteemed schools are collaborating—from Penn Engineering to Penn VET.
In short, sorting out the puzzle of health and disease in the human body starts with Immune Health, and the Abramson Cancer Center is driving this new frontier.
Immune Health is galvanizing Penn researchers and scientists to take immunology to the next level. It’s leveraging the Abramson Cancer Center’s position as a leader in medical care and research to helm the deployment of routine human immune profiling for real time clinical decision-making—an impact that will be felt across all medical disciplines, not just cancer.
E. John Wherry, PhD, Chair of Systems Pharmacology and Translational Therapeutics and Director of the Institute for Immunology, has been investigating immune responses in patients critically ill with COVID-19. His goal: To better understand patients’ immune responses—from no response to controlling the virus to causing damage to healthy tissue. Not only does he share these insights with front-line clinicians in real time, he also uses these data to push immunology research forward.
Dr. Wherry and colleagues collected samples from COVID-19 patients—including a cohort with cancer—then used Immune Health to answer questions related to intensity and type of immune response. The results helped clinical teams interpret and better understand the symptoms they were seeing in patients.
The research showed three distinct immune responses to the SARS-CoV2 infection—patterns that can help predict the trajectory of the disease and inform how best to treat patients.
While early studies revealed details on the immune response to the virus, most had been single-case reports or focused on a small group of patients. Dr. Wherry’s study is the first comprehensive immune profile of a large number of hospitalized patients. Importantly, 65% of the cohort was African American, accurately reflecting a demographic of those most impacted by the virus - and who could benefit from advanced care.
Dr. Wherry’s work is also shaping future vaccine strategies. His research revealed people who recovered from COVID-19 had a strong antibody response after the first mRNA vaccine dose and that antibody response did not increase after the second dose. He found those who did not previously have COVID-19 did not have a full immune response until after the second vaccine dose, suggesting a two-dose strategy is the most effective at providing protection from the virus. Their work is helping inform ways to prevent disease in immunocompromised patients—from cancer to COVID-19 to multiple sclerosis.
Dr. Wherry, who also co-leads the Abramson Cancer Center’s Immunobiology Research Program, credits the collaborative spirit at Penn Medicine for these breakthroughs. "The beautiful thing about Penn is how quickly people with [different types of] expertise stepped in, contributed knowledge, put their feet to the ground, started doing experiments and started helping to set up experiments. The community has been acting as a real team bringing everything to bear on this."
It demonstrates what is possible with science, and how vital it is to invest in ongoing medical research and academic institutions such as the Abramson Cancer Center and Penn Medicine.
Watch Penn Scientists Discuss Immunology and COVID-19
Martha and Peter Morse’s $1.5 million gift to Penn Medicine was the first step toward building the foundation of a years-long visionary project. The goal: To catalyze studies into immune fitness. Better understanding immune fitness—our body’s level of resilience and ability to adapt to challenges the body faces—will enhance our ability to exploit this knowledge to our advantage.
The philanthropic investment is integral to Immune Health Discovery. The Morse’s generosity helps researchers collect, bank and examine samples of blood from patients with lymphoma; monitor patient outcomes; innovate technical advances; and establish a fundamental body of data that can be leveraged to publish findings and take promising results into more diseases—from cancer to COVID-19.
Researchers at the Abramson Cancer Center are finding innovative ways to build on and improve the efficacy of cancer immunotherapies in Penn’s collaborative environment. Scientists are working together on creative combinations of therapies that exploit the immune system to improve treatments for pancreatic, breast and many other cancers.
Pancreatic cancer accounts for approximately 3% of all cancer diagnoses in the United States, but it is the third most common cause of cancer-related death. Because immune checkpoint inhibitors used for other cancers are largely ineffective for patients with pancreatic cancer, and screenings and early detection methods do not yet exist, it is also notoriously difficult to treat. However, there is hope that cell therapy could play a key role in changing this dynamic and help make strides in the diagnosis and treatment of pancreatic cancer.
The research of Mark O’Hara, MD, Assistant Professor of Medicine, focuses on bringing novel immunotherapies to patients with pancreatic cancer through clinical trials. In collaboration with the Parker Institute for Cancer Immunotherapy, which helps fund research across the nation to accelerate the development of breakthrough immunotherapies, Dr. O’Hara tested a combination of a checkpoint inhibitor, an experimental CD40 antibody and chemotherapy in patients with metastatic pancreatic adenocarcinoma. Although still early phase, results were promising, with 83% of patients seeing tumor shrinkage. For the stage four pancreatic cancer patients on the trial—several of whom underwent therapy for more than a year—going from a two- to six-month survival outcome to spending any amount of time with friends and family is an immeasurable opportunity.
Through the support from a Stand Up to Cancer-Lustgarten Foundation grant, the team is also evaluating CAR-T cell therapy in patients with refractory pancreatic cancer both as a single agent as well as in combination with other novel immunotherapies such as oncolytic adenoviruses. These novel treatment approaches hold promise for bolstering the potential of one’s own immune system in the treatment of pancreatic cancer.
"What’s changed is the dimension of hope. The pace of discovery takes your breath away," says Carl June, MD. "It’s a brand new world."
Immunotherapy may hold the answer to expanding our ability to provide the most effective options for our breast cancer patients. Penn Medicine breast surgeon, Julia Tchou, MD, PhD, FACS, launched a clinical trial called BreastVax to explore whether a single dose of immunotherapy—or immunotherapy with radiation therapy—before surgery eliminates the disease at an early stage. Her work on this front was inspired by a patient with metastatic melanoma for whom immunotherapy was not working. After being given radiation therapy to relieve pain, his tumors shrank. Researchers believe the radiation therapy made the unresponsive tumor cells vulnerable to the effects of immunotherapy. They are now exploring the potential of this discovery for breast cancer patients.
Doug Olson, a CAR T Clinical Trial participant, recently celebrated his 75th birthday — in remission.
In 2017, the FDA approved CAR T-cell therapy, making it the first FDA-approved personalized cellular therapy for cancer. In the ensuing years, strides have been made in the treatment of multiple cancers using CAR T-cell therapy. Here is a snapshot of just some of these advancements.
Penn’s Center for Cellular Immunotherapy continues to refine Penn-discovered CAR T-cell therapy to treat more blood cancers. Now more than 10 years after initial infusions, new research published in Nature points to prolonged remission in patients treated with CAR T-cell therapy for chronic lymphocytic leukemia. Summer 2022 marked an additional approval of the FDA-approved therapy, Kymriah®—this time for use in patients with relapsed or refractory follicular lymphoma—its third indication since 2017.
Doug Olson was only 49 and had always been healthy until 1996, when he was diagnosed with chronic lymphocytic leukemia. Six years went by without the cancer progressing. Then it started to grow. He went through treatment, but the cancer kept coming back.
Doug was facing a situation with very few options when his oncologist, David Porter, MD, Jodi Fisher Horowitz Professor at Penn’s Abramson Cancer Center, offered him a chance to be among the very first patients to try something unprecedented, known as CAR T-cell therapy.
In 2010, Doug became the second of three patients to get the new treatment—and today, 10 years later, he is still cancer-free.
Dr. Porter shares Penn’s forward-thinking approach that reflects the very reason therapies like CAR T exist for patients like Doug and Bill Ludwig, the first CAR T patient, who sadly passed away from COVID-19. "We often say that we learn something from every patient we treat with these therapies, and Bill and Doug, in particular, have given us so many clues that keep us focused on the next generation of personalized therapies."
Donald M. O’Rourke, MD, and his research team are at the forefront of utilizing CAR T-cell therapy to target glioblastoma. In the first-in-human Phase 1 clinical trial, Dr. O’Rourke and his team proved that CAR T-cell therapy is safe for recurrent glioblastoma, and second-generation trials are underway.
With more than 80% of ovarian cancers being diagnosed at advanced stages, it remains the most lethal form of gynecologic cancer and there have been few significant advancements in treatment for 30 years. Daniel Powell, PhD, Associate Professor of Pathology and Laboratory Medicine, and Payal Shah, MD, Assistant Professor of Medicine, are working to change that by advancing studies of CAR T-cell therapies in women with recurrent ovarian cancers. The team identified a highly promising target for CAR T-cell therapy—the protein alpha folate receptor (aFR), which is expressed in 80-90% of ovarian cancers. They have successfully created and administered these aFR-specific CAR T cells in several cohorts of patients in an effort to trigger anti-tumor immunity and achieve clinically meaningful tumor responses. Results have been promising.
Scientists in the beginning of their careers have the power to transform the lives of patients and accelerate cancer cures. From piloting trials of novel treatments to digging into fundamental questions in the field of cancer research, these scientists spur innovation.
One such investigator recently made a key discovery in melanoma. Thanks to early funding from the Tara Miller Melanoma Foundation, Abramson Cancer Center researcher and lead study author, Alexander Huang, MD, Assistant Professor of Medicine, showed how a single dose of PD-1 inhibitor before surgery for melanoma can put patients in remission.
Dr. Huang and his team gave 27 patients one dose of the PD-1 inhibitor pembrolizumab three weeks before surgery. Eight of the 27 had a complete response or a major response, meaning less than 10% of the cancer cells remained at the time of the surgery.
Dr. Huang’s study comprised the largest cohort of patients to be treated with anti-PD-1 drugs before surgery. Patients completed up to a year of anti-PD-1 therapy after surgery, and those with complete responses after the initial dose remained cancer-free for more than two years.
The research also demonstrated immune responses brought on by this therapy peaked as early as seven days after treatment, which is much earlier than previous studies have shown.
Alexander Huang, MD
Dr. Huang, who is also a Bridge Scholar through the Parker Institute for Cancer Immunotherapy, believes these critical data can help inform the best path forward when it comes to utilizing new cancer therapies and improving outcomes—especially for melanoma, which is the deadliest form of skin cancer.
Additionally, the researchers identified patterns in the way melanoma that comes back after surgery can adapt to develop resistance to PD-1 inhibitors, offering even more insight into how to treat patients effectively. The early outlook for this novel therapy is encouraging, and Dr. Huang and his team will continue to explore its potential.
