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PHILADELPHIA (February 15, 2021) – Researchers at Fox Chase Cancer Center have helped to identify a cellular resilience mechanism through which acute myeloid leukemia (AML) cells survive cancer treatment and repopulate leukemia, causing disease relapse. The research also suggests that certain drugs could be used to destroy these treatment-surviving AML cells. Cihanger Duy, PhD, MS, assistant professor in the Cancer Signaling and Epigenetics Program at Fox Chase, who led the study, made an early observation in his postdoctoral research that AML cells adopt a dormant senescent-like state in response to chemotherapy that has the potential to repopulate leukemia. Senescence, another word for cellular aging, is the point at which cells lose their ability to divide and grow. The study, “Chemotherapy Induces Senescence-Like Resilient Cells Capable of Initiating AML Recurrence,” was published in Cancer Discovery, a journal of the American Association for Cancer Research. Duy’s findings revealed a new drug resilience mechanism that AML cells use to recover once hit by cancer treatment, unlike drug resistance in which cancer cells acquired features that shield them from treatment. Past studies suggested that AML relapse was caused by the presence of inherently more resistant leukemia stem cells, Duy said. “The concept arose from the observation that there is a hierarchy of leukemia cells, and at the top are immature leukemia stem cells that are drug resistant. After chemotherapy, people thought that the treatment killed mature leukemia cells, but immature leukemia stem cells survived.” Instead, in their study, Duy and colleagues found that when patient-derived AML cells were treated in the lab with chemotherapy, many cells died, but a fraction survived, regardless of whether they were leukemia stem cells. These residual cells were large, stopped growing, and showed markers of cellular senescence. “The notion has always been that senescence is a terminal stage, that the cells stop growing,” Duy said. “Seminal work in the 1960s found that cells stopped growing after a certain number of rounds of cell division, but these were normal cells, not AML cells that have acquired mechanisms to bypass senescence.” Entering this senescence-like phase allows AML cells to endure chemotherapy; the phase appears to be temporary. When the AML cells awaken, they are able to begin dividing again. Duy developed new methods to monitor these senescence-like cells over a longer period of time and found that the cells were able to recover from senescence. “We observed that after a certain number of weeks the AML cells escaped senescence,” Duy said. “Our study suggests that there are conserved resilience mechanisms in cells to cope with environmental challenges. AML cells take advantage of these conserved resilience mechanisms to survive chemotherapy.” Duy found that inhibition of the ATR protein kinase, a key factor in cellular DNA damage response, impaired this resilience mechanism, meaning that ATR inhibitors could be an approach for targeting senescence-like cells to prevent recovery of AML after chemotherapy. *** About Fox Chase Cancer Center The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes.

PHILADELPHIA (February 2, 2021) – New research out of Fox Chase Cancer Center has shed light on how an important type of T cell–gamma delta T cells–develop and are assigned their effector function. In a paper published today, David Wiest, PhD, deputy chief scientific officer at Fox Chase, and colleagues have shown that the expression of transcription factor T-cell factor 1 (TCF1) plays a critical role in the separation of two lineages of T cells–alpha beta T cells and gamma delta T cells–and also determines the kind of function that gamma delta T cells will perform. TCF1 is a transcription factor that regulates the expression of genes during T cell development. Unlike in the more commonly occurring alpha beta T cell, the role of TCF1 in gamma delta T cell development remains poorly understood, Wiest said. “There was still a lot to determine as to how this transcription factor works in that cell lineage.” In their study, Wiest and colleagues revealed a novel regulatory axis where T cell receptor signaling controls TCF1 expression through the Tcf7 locus. This axis is what regulates gamma delta T cell development and effector fate. The researchers showed that the level of TCF1 expression played a role in setting the threshold for gamma delta T cell commitment and affecting the ability of T cell receptor signaling to influence effector fate and identified the regulatory element in the TCF1 locus through which expression is controlled. “There was a study published five years ago that demonstrated that the most significant favorable prognostic factor in cancer was the presence of gamma delta T cell in the tumor,” Wiest said. Gamma delta T cells can perform many functions, including production of interferon, which will antagonize cancer growth, and production of interleukin-17, which appears to be involved in promoting cancer progression. According to Wiest, if the level of Tcf7 drops too low it causes gamma delta T cells to become interleukin 7 producing. “By understanding how Tcf7 levels are controlled, we can avoid circumstances where gamma delta cells will make the cancer grow faster and support circumstances to make gamma delta cells that will kill cancer,” he said. The more that is known about how the function of anti-cancer effectors is regulated, the easier it might be to manipulate it for therapeutic benefit. “We think that this work has the potential to pave the way to using genome editing to produce custom anti-cancer effectors that have increased potency,” Wiest said. The study, “The E-protein-TCF1 Axis Controls γδ T Cell Development and Effector Fate,” was published in Cell Reports. *** About Fox Chase Cancer Center The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

All Temple University Hospital campuses – Main, Episcopal and Jeanes – have earned an ‘A’ grade from the Leapfrog Group on its Fall 2020 Hospital Safety Grade report. The Leapfrog Group is an independent nonprofit organization committed to driving quality, safety and transparency in the U.S. health system. “Earning this honor is a meaningful milestone for Temple,” said Michael A. Young, MHA, FACHE, President and CEO of Temple University Health System and Temple University Hospital. “It means a national watchdog organization recognizes our high standards and achievements in delivering dependable care, preventing errors, protecting patients from harm and providing safer health care across all of our campuses.” The ‘A’ grade represents rapid and substantial progress for Temple University Hospital’s Main and Episcopal campuses, which earned a Leapfrog ‘B’ grade last year and a ‘C’ grade the year before; the Jeanes Campus held the reins on an ‘A’ for most of the past several years. In its recognition letter, the Leapfrog Group emphasized that “despite the unprecedented challenges that surround us, your team [at Temple] has demonstrated a continued commitment to patient safety and the reduction of avoidable harm. Your entire faculty and staff should be proud of this achievement.”

Se suele considerar que la excelencia en el trasplante pediátrico tiene un número superior de niños que sobreviven a la cirugía y viven con éxito con su órgano trasplantado durante tres años. Este es el estándar utilizado por la United Network for Organ Sharing (UNOS)* La excelencia clínica se desarrolla a través de la experiencia. Nuestro equipo incluye médicos clínicos, algunos de los cuales participaron en los primeros trasplantes de hígado pediátricos realizados en Estados Unidos. Desde el comienzo, hemos estado comprometidos con el desarrollo de las mejores prácticas en la técnica quirúrgica y con la determinación de qué pacientes necesitan un trasplante y tendrán los mejores resultados. De hecho, uno de los miembros de nuestro equipo elaboró un artículo de referencia* sobre la selección de pacientes que sigue siendo relevante en la actualidad, más de 30 años después de su publicación. Pero hay más en esta historia. En Nemours, la verdadera excelencia significa llevar nuestra experiencia y capacidad a la mayor cantidad de niños posible mediante un mayor acceso a la atención médica. En la actualidad, realizamos 2.5 veces más trasplantes en niños afroamericanos que otros centros, pero aún persisten las barreras para la atención médica. Algunos obstáculos son la pobreza, la escasa disponibilidad de centros de atención médica, la discriminación y las limitaciones de las instituciones médicas, como la falta de experiencia del personal y la reticencia a brindar atención médica a pacientes de alto riesgo. Afortunadamente, hemos mejorado el acceso a trasplantes que salvan vidas mediante nuevas técnicas y esfuerzos de extensión. Mejoramos el acceso mediante nuevas técnicas No hay suficientes donantes pediátricos de hígado para todos los niños que necesitan un trasplante. Uno de nuestros cirujanos ayudó a impulsar un esfuerzo colaborativo para desarrollar técnicas que permiten a los adultos ser donantes vivos para niños pequeños. El método utiliza solo una parte del hígado adulto. Esto significa que los padres u otros parientes compatibles pueden donar una pequeña parte del hígado a un niño. Con este enfoque, hemos reducido casi a cero la cantidad de niños que mueren esperando un hígado en nuestro programa. También promovimos el uso del trasplante de hígado para tratar a niños con tumores hepáticos que no pudieron ser tratados con cirugía o quimioterapia. Nuestros esfuerzos inicialmente fueron recibidos con escepticismo. Pero nuestro éxito, junto con el de otros, condujo a cambios en las políticas que permiten que más niños reciban trasplantes de hígado. Hoy en día, trasplantamos a una mayor proporción de niños con cáncer de hígado en comparación con otros centros y tenemos una de las tasas más altas de éxito de trasplantes en Estados Unidos Pero no nos detuvimos allí. Mejoramos el acceso mediante la extensión y la asociación Hace veinticinco años, nuestro equipo inició un programa de trasplante de hígado en Bolivia capacitando a cirujanos locales. Dos años después, comenzamos un programa similar en la India. Hoy, seguimos iniciando nuevos programas en países donde los médicos clínicos están listos para iniciar el camino para brindar esta atención médica a los niños. ¿Qué es la excelencia en trasplantes pediátricos de hígado? Es tener excelentes resultados para todos los niños que necesitan un trasplante de hígado en cualquier parte del mundo. Es utilizar el siguiente hígado disponible de alta calidad para un niño incluso cuando requiere una cirugía técnicamente exigente y al mismo tiempo tener excelentes resultados y reducir el riesgo de muerte mientras el niño está en la lista de espera. Eso es lo que creemos. Esto es lo que somos. Nos sentiríamos privilegiados por formar parte del recorrido de tu hijo hacia el trasplante de hígado. Conoce a una de nuestras pacientes con trasplante de hígado, Bella Rose*. Referencias y recursos Base de datos SRTR* Base de datos SPLIT* Pediatric liver transplantation: Patient evaluation and selection, infectious complications, and life-style after transplantation (Trasplante de hígado pediátrico: evaluación y selección de pacientes, complicaciones infecciosas y estilo de vida después de un trasplante); actas de trasplantes, septiembre de 1987, 19 (4):3309‑16. *Disponible solo en inglés De la oficina del Dr. Stephen P. Dunn, MD Cirujano de trasplante pediátrico de Nemours Presidente, Departamento de Cirugía de Nemours Email: Stephen.Dunn@nemours.org

Clinical excellence is developed through experience. Our team includes clinicians, some of whom were involved with the earliest pediatric liver transplants, performed in the United States. From the beginning, we have been involved in developing best practices for surgical technique as well as determining which patients need and will do best with transplantation. In fact, one of our team members authored a landmark article on patient selection that is still relevant today, more than 30 years after it was published. But there is more to the story. At Nemours, true excellence means bringing our experience and skill to as many children as possible by increasing access to care. Today, we perform 2.5 times the number of transplants on African American children than other centers, yet barriers to care persist. Poverty, poor availability to health care facilities, discrimination and limitations in medical institutions, such as a lack of staff expertise and a hesitation to care for patients who are high risk, constitute obstacles. Fortunately, we have improved access to life-saving transplants through new techniques and outreach efforts. Improving Access Through New Technique There are not enough pediatric liver donors for all the children who need to be transplanted. One of our surgeons helped to pioneer a collaborative effort to develop techniques that allow adults to be living donors for small children. The method uses only a portion of the adult liver. This means parents or other matched relatives can donate a small portion of their liver to a child. Using this approach, we have nearly eliminated the number of children who died waiting for a liver in our program. We also pioneered the use of liver transplantation to treat children with liver tumors that could not be treated with surgery or chemotherapy. Our efforts were initially met with skepticism. But our success, along with that of others, led to policy changes that allow more of these children to receive liver transplants. Today, we transplant a higher proportion of children with liver cancer compared with other centers and have one of the highest transplant success rates in the United States. But we did not stop there. Improving Access Through Outreach and Partnership Twenty-five years ago, our team started a liver transplant program in Bolivia by training local surgeons. We started a similar program in India two years later. Today, we continue to initiate new programs in countries where clinicians are ready to begin the journey of providing this care to children. What is excellence in pediatric liver transplantation? It is excellent outcomes for all children who need liver transplantation anywhere in the world. It is using the next available, high quality liver for a child even when it requires technically demanding surgery, while delivering excellent outcomes and reducing the risk of dying on the wait list. That is what we believe. This is who we are. We would feel privileged to become a part of your child’s liver transplant journey. Meet one of our liver transplant patients, Bella Rose. References and Resources SRTR Database SPLIT Database Pediatric liver transplantation: Patient evaluation and selection, infectious complications, and life-style after transplantation; Transplantation Proceedings, September 1987, 19 (4):3309-16. From the Desk of Stephen P. Dunn, MD Nemours Pediatric Transplant Surgeon Chair, Nemours Department of Surgery Email: Stephen.Dunn@nemours.org Excellence in pediatric transplantation is commonly regarded as having a superior number of children who both survive surgery and live successfully with their transplanted organ for three years. This is the standard used by the United Network for Organ Sharing (UNOS)

Lankenau Heart Group physician practices, part of Main Line Health’s Lankenau Heart Institute, have been recognized by the American Heart Association (AHA) for their commitment to managing heart disease risk by controlling risk factors like high cholesterol and diabetes. Both awards are a testament to Lankenau Heart Institute’s commitment to the prevention, diagnosis, treatment and management of cardiovascular disease. Sixteen Lankenau Heart Group practices earned the AHA’s Check. Change. Control. Cholesterol Participation award in recognition of the Group’s collective commitment to reducing the risk of heart disease and stroke among patients by promoting tactics to manage cholesterol. To effectively manage cholesterol among patients, Lankenau Heart Group physicians prescribed statins for adult patients who: Had a diagnosis of clinical atherosclerotic cardiovascular disease Had been previously diagnosed or had a family history of high cholesterol Were between ages 40-75 with Type 1 or Type 2 diabetes and an LDL of 70-189 mg/dL Additionally, Lankenau Heart Group at Newtown Square received the AHA’s Target: Type 2 Diabetes Gold Award for implementing quality improvement measures to address the relationship between diabetes and cardiovascular disease in the outpatient setting. The Gold Award recognizes practices that have fulfilled the participant criteria and met the Gold Award level thresholds for each of two selected clinical measures related to diabetes control and cardiovascular disease risk factors, hypertension and high cholesterol. Lankenau Heart Group at Newtown Square was specifically recognized for showing impressive HbA1c control in patients with diabetes. “These well-deserved awards recognize our Lankenau Heart Group physician practices for their ongoing commitment to keeping our patients well by not only following proven guidelines that reduce the onset or recurrence of heart and vascular disease, but also by providing education and guidance to help inform healthy decisions. At Lankenau Heart Institute, we offer advanced surgical and interventional care for complex cardiovascular issues when they arise, but the goal is always to be able to offer early, preventative approaches that reduce the need for those hospitalizations. These awards are a testament to the excellent care being offered at our practices, and we couldn’t be more proud to be receiving them,” says William Gray, MD, System Chief of Cardiovascular Disease at Main Line Health. High cholesterol and diabetes are two of the most common risk factors for heart disease. Nearly one in three American adults have high LDL or “bad” cholesterol and need personalized treatment while every 80 seconds, an adult with diabetes in the U.S. is hospitalized for heart disease. Lankenau Heart Institute offers the full continuum of cardiovascular care: prevention, diagnosis, imaging, treatment, cardiac rehabilitation and disease management at its hospitals and 16 Lankenau Heart Group practices across the region. About Lankenau Heart Institute The Lankenau Heart Institute is Main Line Health’s premier, comprehensive cardiovascular medicine and surgery program. The Lankenau Heart Institute brings together the clinical expertise of all four Main Line Health acute care hospitals and community cardiology practices to ensure that patients receive a level of quality, service, and experience that is unprecedented in the region. Through the system-wide coordination of services, the Lankenau Heart Institute delivers preventive, diagnostic, therapeutic, and rehabilitative cardiovascular services at each of our locations including Lankenau Medical Center, Bryn Mawr Hospital, Paoli Hospital and Riddle Hospital. Lankenau Heart Institute continues to be a pioneer in the use of beating-heart techniques and robotic-assisted procedures for coronary artery revascularization, minimally invasive and transcatheter approaches for valve repair and replacement, and complex aortic surgeries. With our growing experience and focus on minimally invasive techniques, Lankenau Heart Institute has expanded participation in clinical trials year over year. Our physicians are frequently invited to participate in clinical/medical device trials, many of these designed to facilitate minimally invasive procedures/approaches. With a collaborative team of expert consultative cardiologists, interventional cardiologists, electrophysiologists, cardiovascular surgeons and specially trained nurses and technologists, the Lankenau Heart Institute is dedicated to managing and treating patients with heart failure, aortic disease, coronary and peripheral vascular disease, heart rhythm disorders and valve disease. Our team of cardiologists and cardiac specialists provide patients and their families with expert cardiac care, close to home. About Main Line Health Founded in 1985,Main Line Health is a not-for-profit health system serving portions of Philadelphia and its western suburbs. Main Line Health’s commitment—to deliver advanced medicine to treat and cure disease while also playing an important role in prevention and disease management as well as training physicians and other health care providers—reflects our intent to keep our community and ourselves well ahead. A team of more than 10,000 employees and 2,000 physicians care for patients throughout the Main Line Health system. At Main Line Health’s core are four of the region’s most respected acute care hospitals—Lankenau Medical Center, Bryn Mawr Hospital, Paoli Hospital and Riddle Hospital—as well as one of the nation’s recognized facilities for rehabilitative medicine, Bryn Mawr Rehabilitation Hospital. Main Line Health also includes Mirmont Treatment Center for drug and alcohol recovery; Main Line Health HomeCare & Hospice, which includes skilled home health care, hospice and home infusion services; Main Line Health Centers, primary and specialty care, lab and radiology, and other outpatient services located in Broomall, Collegeville, Concordville, Exton, King of Prussia and Newtown Square; Lankenau Institute for Medical Research, a biomedical research organization; and Main Line HealthCare,one of the region’s largest multispecialty physician networks. Main Line Health is the recipient of numerous awards for quality care and service, including System Magnet® designation, the nation’s highest distinction for nursing excellence and the Mid-Atlantic Alliance for Performance Excellence (MAAPE) Excellence Award. Main Line Health is committed to creating an environment of diversity, respect and inclusion and has proudly embraced the American Hospital Association’s #123forEquity Pledge to Act to eliminate disparities in care. We are dedicated to advancing patient-centered care, education and research to help our community stay healthy.

PHILADELPHIA - Jefferson Health, Ambulnz and Philadelphia International Airport (PHL) have announced a partnership to launch a COVID-19 testing program. Starting Friday, Dec. 4, the program will operate from the PHL Terminal E Departures building, and will provide passengers with the confidence they need to travel safely and conscientiously between destinations. The COVID-19 testing program is designed for asymptomatic passengers flying out of PHL, with multiple testing options, including an antigen test, a Polymerase Chain Reaction (PCR) test, and a Rapid PCR test planned in the future. The options range in price from $70 to $130, which distinguishes the PHL program as among the most affordable in the country. Test results will be texted to passengers the same day for antigen tests, and within 48 to 72 hours for the standard PCR test. Parking in the Terminal E Parking Garage will be complimentary for up to 2 hours for testing patrons. The availability of COVID-19 testing will enable PHL to expand connections with destinations requiring testing prior to arrival. Passengers traveling to many Caribbean destinations must produce a negative PCR test result, administered in the previous 72 hours, as a condition for boarding a plane. The Caribbean represents one of PHL’s largest destination markets in the winter season. “Jefferson Health and Ambulnz are ideal partners for this program, because they possess an incredible combination of world-class expertise with a focus on equity in healthcare access,” said PHL CEO Chellie Cameron. “This testing service will enable Philadelphia to safely reconnect passengers to new destinations, supporting the recovery of the entire region.” Medical providers will administer testing in the Terminal E facility, which has been equipped with medically appropriate air filtration and circulation, as well as a private office setting for each passenger. Jefferson Health will administer the testing via Rapid Reliable Testing, the COVID response division of Ambulnz, which is a joint venture with Jefferson. “Jefferson has been here for our community throughout this crisis, and this is a next step in helping people conduct essential travel,” said Stephen K. Klasko, MD, MBA, president of Thomas Jefferson University and CEO of Jefferson Health. "Innovative partnerships work. This partnership with the Philadelphia Airport, our partner Ambulnz, and our ties to Europe give us the opportunity to develop new solutions for economic recovery." The program has been built to scale up as demand increases. Additional testing program locations have been identified at PHL and will be announced when available. Media Contacts: Florence Brown, Philadelphia International Airport , Director of Communications Florence.Brown@phl.org Brandon Lausch, Jefferson Health, Senior Director, News & Media Relations Brandon.Lausch@jefferson.edu Josh Weiss, Ambulnz, Public Relations 1-480-789-0743 josh@10to1pr.com About Jefferson Health Jefferson Health, home of Sidney Kimmel Medical College, is reimagining health care in the greater Philadelphia region and southern New Jersey. Jefferson’s dedicated team of doctors, nurses, health professionals and staff provides a range of primary to highly-specialized care through 14 hospitals (seven are Magnet®-designated by the ANCC for nursing excellence), more than 40 outpatient and urgent care locations, the NCI-designated Sidney Kimmel Cancer Center, Magee Rehabilitation and the JeffConnect® telemedicine program. For 2020-2021, Thomas Jefferson University Hospitals is ranked among the nation’s best hospitals in nine specialities by U.S. News & World Report. Jefferson Health’s mission is to improve the lives of patients in the communities it is privileged to serve through safe, effective, equitable, compassionate care. About Ambulnz Ambulnz is a leading provider of mobile medical services and medical transportation in the U.S. and UK. Ambulnz’s TeleHealth+ provides non-emergency medical services to patients in their homes, delivering the full promise and potential of telemedicine. Their experienced medical field staff of more than 1,500 EMTs, paramedics, and licensed practical nurses work under the guidance of MD1 Medical Care PC to fill the gap between a visit to the doctor’s office and a traditional telemedicine call. Ambulnz uses disruptive, AI-powered technology to dispatch and manage their fleet, and is the only medical transportation company that offers ambulance, ambulette, and medical sedan options to accommodate every type of patient need. Their Rapid Reliable Testing division has already tested over 500,000 individuals for COVID-19, helping manage the spread of the pandemic. Ambulnz is the largest private ambulance company responding to COVID-19 in New York City and has transported over 15,000 COVID-19 patients nationally. For more information about Ambulnz, visit www.ambulnz.com or follow them on Facebook, Twitter, Instagram and LinkedIn. About Philadelphia International Airport Philadelphia International Airport is owned and operated by the City of Philadelphia. The airport is a self-sustaining entity that operates without the use of local tax dollars. It is one of the largest economic engines in Pennsylvania, generating an estimated $16.8 billion in spending annually and supporting more than 106,000 full-time jobs for the 11-county Philadelphia metropolitan statistical area.

PHILADELPHIA (November 17, 2020)—Patients with mantle cell lymphoma treated at Fox Chase Cancer Center will now have access to treatment with brexucabtagene autoleucel, also known as Tecartus, the first cell-based gene therapy approved by the Food and Drug Administration (FDA). Tecartus, a chimeric antigen receptor (CAR) T-cell therapy, was approved for adults with mantle cell lymphoma who have not responded to or who have relapsed following other kinds of treatment. Fox Chase is a certified treatment center for the therapy. With CAR T therapy, patients’ T cells are collected and genetically modified to include a new gene that facilitates the targeting and killing of lymphoma cells. These modified T cells are then infused back into the patient. “This is probably one of the most promising therapies for patients with mantle cell lymphoma, including those with a type of disease called P53-mutated mantle cell lymphoma,” said Henry Chi Hang Fung, MD, FACP, FRCPE, chair of the Department of Bone Marrow Transplant and Cellular Therapies at Fox Chase. Fung was an investigator on the clinical trial that led to the FDA’s approval of Tecartus. The ZUMA-2 trial looked at the safety and efficacy of the therapy in patients with relapsed or refractory mantle cell lymphoma and found that 87% of participants responded to a single infusion of the therapy. All signs of cancer disappeared—a complete response—in 62% of patients. “A complete response rate of greater than 60% with Tecartus is even better than responses seen with first-line treatment after the initial diagnosis,” Fung said. “It is a very effective treatment.” Mantle cell lymphoma is an uncommon lymphoma occurring in cells originating in the mantle zone of the lymph node. These lymphomas comprise only a small percentage of cases of non-Hodgkin lymphoma diagnosed each year, Fung said. Patients diagnosed with the disease will typically undergo initial treatment with chemotherapy or a stem cell transplant. However, even with transplant the disease will recur. In recent years, several Bruton’s tyrosine kinase (BTK) inhibitors—acalabrutinib, ibrutinib, and tozanubrutinib—have been approved for patients with mantle cell lymphoma who have received at least one prior line of therapy. “When patients failed these treatments, even after having durable responses, we had nothing to offer them,” Fung said. “The responses we are seeing with Tecartus are like nothing we have seen in the history of mantle cell lymphoma.” Fox Chase also provides FDA-approved CAR T therapy for relapsed or refractory large B-cell lymphoma in adults and refractory B-cell precursor acute lymphoblastic leukemia in young adults up to 25 years old. The effectiveness of cellular immunotherapy against other hematologic malignancies is also being explored. At Fox Chase, a variety of clinical trials are focused on multiple myeloma, follicular lymphoma, and chronic lymphocytic leukemia. *** About Fox Chase Cancer Center The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach.

PHILADELPHIA (November 5, 2020) – Researchers at Fox Chase Cancer Center have harnessed the power of the Nobel Prize-winning CRISPR/Cas9 technology to identify cellular factors involved in resistance to sunitinib by clear cell renal cell carcinoma. Renal cell carcinoma is the most common type of kidney cancer and the tyrosine kinase inhibitor sunitinib is a drug that is a standard front-line therapeutic agent for the treatment of advanced disease. However, sunitinib doesn’t work for some patients with renal cell carcinoma and even those patients who initially respond to the drug will eventually develop resistance. Peter Makhov, MD, PhD, a research assistant professor at Fox Chase, developed the idea of using CRISPR/Cas9-based high-throughput loss-of-function screening to identify factors involved in cell resistance to sunitinib. Using this method, Makhov, who at the time of the study worked in the lab of Vladimir Kolenko, MD, PhD, an associate research professor in the Cancer Biology program, and colleagues identified the critical role of a protein called farnesyltransferase as a contributing factor of resistance to sunitinib. “On a genetic level we can knock down the expression of farnesyltransferase, which sensitized the cancer cells to sunitinib, but to treat people, the next step was to figure out if we have any inhibitors of farnesyltransferase,” Kolenko said. “We were lucky that there are commercially available pharmacological inhibitors of farnesyltransferase that are used in the treatment of progeria.” When the farnesyltransferase inhibitor lonafarnib and sunitinib were combined to treat renal cancer cell lines, there was a synergistic response called synthetic lethality. Kolenko and colleagues are researching how this mechanism of resistance works. “We believe that tumor cells can accumulate sunitinib in specific organelles called lysosomes,” he said. “Eventually the concentration of sunitinib is really high and resistance occurs.” When combined with lonafarnib, the lysosomal sequestration of sunitinib was disrupted and the drug can again act as an inhibitor. “That is why combination therapy with sunitinib and lonafarnib is much more potent than treatment with sunitinib alone,” Kolenko said. This new CRISPR/Cas9 loss-of-function approach can be used to identify resistance mechanisms for any drug, he added. “We plan to use the same approach for identifying potential genes whose inactivation is synthetically lethal in combination with other targeted therapeutics,” Kolenko said. “This gives us a very powerful tool.” The paper, “CRISPR/Cas9 Genome-Wide Loss-of-Function Screening Identifies Druggable Cellular Factors Involved in Sunitinib Resistance in Renal Cell Carcinoma,” was published in the British Journal of Cancer.

PHILADELPHIA (November 4, 2020)—Fox Chase Cancer Center has become the first cancer center in the Northeast to feature a new tumor marker technology that has been described as the next generation of surgical navigation, one that will make breast excisional biopsies and breast-conserving surgeries more precise. Breast surgeons have had few tools available to guide them in the removal of cancerous breast tissue, but with the EnVisio real-time Surgical Navigation System and SmartClip Tumor Marker technology, surgeons will be better able to navigate to the precise location of malignant breast tissue during a lumpectomy, significantly advancing breast care. “The EnVisio navigation system is a step up from other technologies on the market for localization of tumors because it shows the tumor relative to the detector in three dimensions on a screen, making it easier for the surgeon to assess where the tumor is and how best to resect it,” said Richard J. Bleicher, MD, FACS, a professor in the Department of Surgical Oncology at Fox Chase. Bleicher said the intelligence of the SmartClip marker partnered with the real-time surgical navigation system is a key feature of the technology. “Most localization devices provide solely a distance between the tip of the detector and the clip placed in the patient, but don’t provide directionality. This provides distance and a view of where the clip is in the patient relative to the detector in three dimensions.” Bleicher believes the technology will greatly benefit patients. “Because the surgeon can see the clip relative to the detector in three dimensions, it should shorten times for resection, limiting anesthesia time for the patients,” he said. “It will enable smaller and more accurate resections, sparing unnecessary breast tissue removal, and because the SmartClip can be placed in the tumor in advance, it eliminates delays and patient waiting on the day of surgery,” Bleicher added. The wireless SmartClip Soft Tissue Markers are placed in the breast or other soft tissue to mark the location of the tissue to be removed at the time of breast biopsy or any time prior to tumor-removal surgery. During surgery, the SmartClip and the EnVisio Navigation system guide the surgical removal of cancerous tissue. The system’s real-time 3D rendering helps surgeons navigate their tools directly to the tumor to remove the affected tissue, something akin to surgical GPS. The system is made by Elucent Medical. Lee Wilke, MD, the company’s co-founder and director of the University of Wisconsin Breast Center, helped develop the technology, which she describes as “next-generation surgical navigation.” One of the goals of developing the technology was sparing millions of women undergoing breast cancer treatment the additional pain and stress from traditional wire-placement procedures, she said. “My hope is that in the near future, women will be able to move quickly through the pathway of diagnosis to surgery, while improving patient outcomes. Having the SmartClip placed prior to the day of surgery and the precision navigation in the operating room is delivering improved care pathways for our breast cancer patients,” Wilke said. “For decades, there has been minimal innovation in breast conserving surgery,” said Laura G. King, CEO of Elucent. “We are honored to be partnering with Fox Chase Cancer Center, a leader in cancer care, to bring precise surgical navigation into the hands of their skilled surgeons.”

PHILADELPHIA (October 23, 2020) – Researchers at Fox Chase Cancer Center have discovered a potential new target in the treatment of endometrial carcinoma, thanks in part to generous funding from Peggy’s Pathway for Women’s Cancer Care. The research was published recently in Molecular & Cellular Proteomics. Using a technology called multiplexed inhibitor beads and mass spectrometry, James S. Duncan, PhD, associate professor in the Cancer Biology research program at Fox Chase, and colleagues profiled the kinome of endometrial tumors and normal endometrial tissues and identified a network of kinases that were overexpressed, including serine/arginine-rich splicing factor kinase 1 (SRPK1). “This project really sums up the concept of a lot of the work that Fox Chase is trying to do when it comes to research,” Duncan said. “Peggy’s Pathway selected our project for funding because they thought our approach of looking at kinase signaling looked interesting, and, as a result, we have found something that may be actionable.” Peggy’s Pathway for Women’s Cancer Care is a charity started in honor of Peggy Pettinato, who passed away from serous endometrial carcinoma. The organization’s mission is to raise funds for research into innovative treatments and early detection of endometrial cancer, the most common gynecologic malignancy in the United States. According to Duncan, endometrial tumors frequently have alterations in protein kinases, a family of about 535 enzymes that are collectively termed the kinome. Kinases are altered in about one-quarter of all cancers and are considered highly susceptible to treatment with drugs because of their catalytic activity. However, only a small fraction of the kinome has been explored therapeutically. Multiplexed inhibitor beads and mass spectrometry is a chemical proteomic strategy that allows researchers to simultaneously look at kinase levels in cells and tumors. “From a cancer standpoint we can identify protein kinases that are up- or downregulated in cancer,” Duncan said. “Ones that are upregulated are of interest because protein kinases play a role in cancer growth, survival, and metastasis, so they often represent potential targets.” The analysis showed that SRPK1 was overexpressed in endometrial cancer tissues and that this overexpression was associated with poor survival, suggesting that SRPK1 could be involved in key tumor-associated properties, Duncan said. “We also discovered that in combination with therapy targeting growth factors—in this case EGFR—targeting this kinase produced strong drug synergy to kill these tumors,” Duncan said. This synergy was found for endometrioid cell lines and uterine serous cancer cell lines, a disease subtype with poor outcomes. To further explore the role of SRPK1, Duncan and colleagues want to apply proteomic technology to try to understand more about how SRPK1 works and conduct experiments to see if EGFR and SRPK1 inhibition has an effect on endometrial cancer tumor models. Peggy’s Pathway now has the goal of raising at least $200,000 over the next two years to fund some of this additional research at Fox Chase. The paper, “Kinome Profiling of Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As Candidate Therapeutic Target,” was published in Molecular & Cellular Proteomics. *** About Fox Chase Cancer Center The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach.

TEMPLE UNIVERSITY HOSPITAL RECENTLY PERFORMED PENNSYLVANIA’S FIRST POST-FDA APPROVAL LUNG TRANSPLANT USING TRANSMEDICS ORGAN CARE SYSTEM FOR LUNG Temple University Hospital (TUH) recently became the first hospital in Pennsylvania to perform a breathing lung transplant using the TransMedics Organ Care System for Lung, or OCS™ Lung, following U.S. Food and Drug Administration (FDA) approval of the device for both standard and expanded criteria donor lungs. The OCS Lung is a portable technology designed to keep organs functioning and “breathing” in an environment that mimics the human body from the time they are removed from the donor until they are implanted in the recipient. The newest FDA approval expands the use of this technology to donor lungs initially deemed unacceptable for procurement and transplantation based on limitations of cold static preservation. The OCS Lung System allows medical teams to place donor lungs in a warm, sterile chamber that provides nutrient-rich and oxygenated blood to perfuse donor lungs while still at the donor hospital. “Temple is able to serve a high volume of lung transplant patients, but tens of thousands of people in the U.S. are currently in need of lifesaving organs,” said Yoshiya Toyoda, MD, PhD, William Maul Measey Chair of Surgery at the Lewis Katz School of Medicine at Temple University (LKSOM) and Chief of Cardiovascular Surgery at TUH. “The hope is that advances in technology like the OCS Lung System will eventually afford more patients the opportunity to receive an organ transplant.” The OCS Lung System allows medical teams to place donor lungs in a warm, sterile chamber that provides nutrient-rich and oxygenated blood to perfuse donor lungs while still at the donor hospital. Through a built-in ventilation circuit in the OCS Lung System, donor lungs will continue to breathe, allowing the medical team to recruit and optimize ventilation throughout the retrieval with no delayed or added time to the retrieval process. The current standard of care for preserving lungs prior to transplant is cold storage. However, the OCS Lung System reduces the time during which the donor lungs are cut off from blood and oxygen support outside of the body. The donor lungs remain in the OCS Lung System perfused and ventilated during transport and until they are ready to be implanted in the organ recipient. In addition to preserving the lungs, the device measures and displays real-time data regarding the health of the organs. Temple University Hospital performed more lung transplants than any other hospital in the nation in 2017, 2018 and 2019. Temple’s Lung Transplantation Program and the nationally recognized Temple Lung Center are comprised of physicians, nurses, therapists, pharmacists, social workers, laboratory technicians and administrative and support personnel who work around the clock to provide cutting edge medical and surgical care to patients with complex and advanced lung disorders. “The Temple Lung Center is able to offer its patients access to some of the most advanced treatments and clinical trials available in the areas of prevention, diagnosis and treatment of complex lung disease,” said Francis Cordova, MD, Professor of Thoracic Medicine and Surgery at LKSOM and Medical Director of the Lung Transplantation Program at TUH. “Temple’s Lung Transplantation Program is one of the nation’s most active, experienced and innovative, regularly providing lifesaving transplants in some of the most challenging cases,” said Norihisa Shigemura, MD, PhD, Professor of Surgery at LKSOM and Surgical Director of the Lung Transplantation Program at TUH. “This innovative technology is state-of-the-art in its ability to preserve the health of the organ in such a small chamber and to ventilate in real-time before the organ is implanted in patients, says M. Abul Kashem, MD, PhD, a Research Faculty and Assistant Professor of Surgery at LKSOM who oversees Temple’s use of the OCS Lung. “Our team is looking forward to seeing the future results of such device-based lung transplant technology that benefits waiting list patients.” Dr. Kashem, along with the surgical and medical team, will analyze survival outcomes for cases in which the OCS Lung technology is utilized, and will also assess long-term benefits for patients. Editor’s Note: Neither Dr. Toyoda, Dr. Cordova, Dr. Shigemura, Dr. Kashem nor any member of their immediate families has financial interest in TransMedics.