FDA Approves Personalized Cellular Therapy Developed by Penn and CHOP for Advanced Leukemia
In a landmark decision for the field of cancer immunotherapy, the U.S. Food and Drug Administration (FDA) approved a personalized cellular therapy at the end of August. It was developed by the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. The approval was granted to Novartis for the chimeric antigen receptor (CAR) T-cell therapy, Kymriah™ (tisagenlecleucel, formerly CTL019). In 2012, Penn and Novartis entered into a global collaboration to further research, develop and commercialize Kymriah and other CAR-T cell therapies for the treatment of cancers. Kymriah is the first therapy based on gene transfer approved by the FDA.
Investigators at Penn’s Perelman School of Medicine and CHOP, who together led research, development and clinical trials of the new therapy in collaboration with Novartis, hailed the FDA’s approval as a game changer for the treatment of younger patients battling the aggressive blood cancer and a pivotal milestone in this new era of cellular therapies that treat cancer with a patient’s own immune system.
“This is a turning point in the fight against B-cell ALL that opens up opportunities for patients across the world who desperately need new options,” said Carl H. June, the Richard W. Vague Professor in Immunotherapy in the department of pathology and laboratory medicine in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center.
“We’re excited and proud to have moved this CAR therapy, in collaboration with Novartis and CHOP, through all phases of development and clinical trials, established its efficacy, and now extended its reach to children across the country under this FDA approval,” Dr. June added. “We hope the momentum behind the technology builds as we continue to investigate the abilities of personalized cellular therapeutics in blood cancers and solid tumors to help patients with many other types of cancer.”
Kymriah is expected to be available through a network of certified treatment centers throughout the United States.
“We delivered engineered T-cell therapy at CHOP for the first pediatric patient in the world, Emily Whitehead, who was only six years old when her leukemia stopped responding to conventional treatments. Emily’s cancer remains in remission, and in larger trials, we’re seeing overall remission rates over 80 percent, which is a remarkable improvement upon previous treatment success rates,” said lead investigator of the CHOP and global trials of the therapy, Stephan A. Grupp, the Yetta Deitch Novotny Professor of Pediatrics at Penn and director of the Cancer Immunotherapy Frontier Program and chief of the section of Cell Therapy and Transplant at CHOP.
The new treatment modifies patients’ own immune T cells, which are collected and reprogrammed at the Novartis manufacturing facility to potentially seek and destroy the patients’ leukemia cells. After being infused back into patients’ bodies, these newly built “hunter” cells both multiply and attack, targeting cells that express a protein called CD19. Tests reveal that the army of hunter cells can grow to more than 10,000 new cells for each single engineered cell patients receive, producing high remission rates in completely refractory leukemia—and can survive in the body for years.
“This transformational therapy for patients is the result of true collaboration between industry, academia, healthcare professionals, patients and caregivers” said Bruno Strigini, CEO, Novartis Oncology. “We thank all those involved in this historic FDA approval, which provides renewed hope to children and young adults who have had limited treatment options thus far.”
CTL019 was first tested at Penn in 2010, in adult patients with advanced chronic lymphocytic leukemia (CLL). In 2012, CHOP became the first institution to investigate Kymriah in pediatric patients with ALL, the most common childhood cancer. About 20 percent of the 3,500 pediatric and young adult patients diagnosed every year with ALL in the United States relapse or do not respond to conventional treatment.
Those early-stage clinical trials, in which more than 90 percent of patients achieved a complete remission one month after receiving the therapy, led to a global registration trial in 2015, involving 68 children and young adults with advanced ALL treated at 25 centers across the world. Eighty-three percent of the patients who received a single dose of their own engineered cells achieved a complete remission.
In July 2017, an FDA advisory panel unanimously recommended approval of the therapy, paving the way for the FDA approval. After presentation of trial data and testimony from families whose children have received the therapy, one expert on the panel said this was “the most exciting thing I’ve seen in my lifetime.”
Many patients in the ALL trials experienced a side effect called cytokine release syndrome (CRS) including grade 3 or grade 4, which includes varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain, and temporary neurologic symptoms, including delirium, but also low blood pressure and breathing difficulties requiring ICU-level care in the most severe cases. Eighteen percent of patients experienced grade 3 or grade 4 neurologic events. Patients were treated with the immunosuppressant drug tocilizumab or short courses of steroids to combat the symptoms.
Novartis will create a registry to follow patients for 15 years after being treated to monitor their progress and any potential future side effects.
Other trials with CTL019 therapy are also underway in the Abramson Cancer Center for adult ALL patients and those with CLL and non-Hodgkin lymphoma. Penn and Novartis are also investigating the next generation of CAR therapies for multiple myeloma, and for solid tumors, through trials in glioblastoma, mesothelioma, and ovarian and pancreatic cancer. Other CAR trials at Penn are exploring the technique for prostate cancer, melanoma and triple-negative breast cancer.
The Novartis-Penn Center for Advanced Cellular Therapeutics (CACT) opened in 2016 and hosted Vice President Joe Biden at the launch of his Cancer Moonshot initiative (Almanac January 26, 2016), cementing Penn’s role as an international innovator in the development and manufacturing of personalized cellular therapies.
Additional leaders of the research include Penn’s David Porter, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the ACC; Noelle Frey, an assistant professor of hematology-oncology; Bruce Levine, the Barbara and Edward Netter Professor in Cancer Gene Therapy in the department of pathology and laboratory medicine; Michael Milone, an associate professor of pathology and laboratory medicine; and CHOP pediatric oncologist Shannon Maude, an assistant professor of pediatrics.
Adult patients who are interested in T cell therapies at Penn Medicine can call (215) 316-5127 for more information.
For information about the Cancer Immunotherapy Program at CHOP, please call (267) 426-0762.
Editor’s Note: The University of Pennsylvania has licensed some technologies involved in these studies to Novartis. Some of the scientists involved in these trials are inventors of these technologies. As a result of the licensing relationship with Novartis, the University of Pennsylvania receives significant financial benefit, and some of these inventors have benefitted financially and/or may benefit financially in the future.
Statement from Penn President Amy Gutmann on the Repeal of DACA
September 5, 2017
This is a heartbreaking day for our country. President Trump’s decision to repeal the DACA program threatens hundreds of thousands of young people who were raised in America, love this country and are an integral part of the American Dream. We know the Dreamers to be gifted and successful students who have grown up in our communities, attended our schools, and who are poised to make vital contributions to our nation’s economic strength, creativity, and global competitiveness. The repeal of DACA will mean the loss of hundreds of thousands of jobs in the United States and hundreds of billions of dollars in economic growth over the next decade. In addition, the direct impact of repeal and deportation will cost tens of billions of dollars. Because this is a matter of grave urgency for our country, I respectfully call upon Congress to act promptly to pass bipartisan legislation to permanently protect the Dreamers. This is both the humane and wise thing to do.
At Penn, we are committed to providing a safe and welcoming environment for all of our students and we will do everything we can to support and assist the Dream Act students who are valued members of our community.
In the newly released 2018 US News & World Report rankings of colleges and universities, Penn is once again ranked eighth overall among national universities.
The Wharton School of the University of Pennsylvania has retained its #1 post as the best undergraduate business program in the country, which it has held for many years. It is also ranked #1 in four specialties: finance, insurance/risk management, marketing and real estate; it ranked #2 in three specialties: international business, management and production/operations management; #3 in quantitative analysis/methods; #4 in accounting and #5 in entrepreneurship.
Penn’s School of Engineering and Applied Science was listed #25 (tied with Harvard, University of Maryland-College Park, University of Minnesota-Twin Cities and University of Southern California) for engineering schools whose highest degree is a doctorate.
Penn made the list of national universities with the largest proportion of international undergraduate students in the 2016-2017 academic year with 12 percent.
Reappointment of Vice Provost for Research Dawn Bonnell
Provost Wendell Pritchett announces the reappointment of Vice Provost for Research Dawn Bonnell, who was initially appointed to a five-year term in 2013 (Almanac July 16, 2013).
“As I begin my tenure as Provost,” said Provost Pritchett, “I am delighted that Dawn Bonnell has agreed to extend her service to the Penn community. A pioneer in nanotechnology and the founding director of Penn’s Nano/Bio Interface Center, Dawn is one of our most vital and admired research leaders. Over the past four years, her leadership and vision have driven enormous progress in this essential area of our mission. She has worked across the University in establishing the Penn Center for Innovation, developing the Pennovation Center, and supporting the evolution of Pennovation Works, which are central to fostering innovation at Penn—and across the entire Philadelphia region. She has led our parallel efforts to diversify the University’s research portfolio, creating stronger partnerships with industry, seeding emerging research areas, and encouraging startups and spinouts that bring the impact of Penn research to a wide public audience.”
Vice Provost Bonnell is the Henry Robinson Towne Professor in the School of Engineering & Applied Science. As Vice Provost for Research, she develops and implements policies that promote research excellence across the University; manages key elements of the University’s research infrastructure, including grant administration and research compliance; and guides the strategic efforts of the University in advancing research commercialization. She also serves as a champion for the research enterprise at Penn, leading research collaborations across Schools, exploring new areas for research and representing Penn to local, regional and national constituencies.
Report of the Ad Hoc Consultative Committee for the Selection of a Provost
The Ad Hoc Consultative Committee for the Selection of a Provost was convened by President Amy Gutmann on December 14, 2016. During its four months of work, the full Committee met on 10 occasions and reported its recommendations to the President on April 13, 2017. The Committee members were:
J. Larry Jameson, Executive Vice President of the University for the Health System, Dean of the Perelman School of Medicine, and Robert G. Dunlop Professor, PSOM
Sigal Ben-Porath, Professor, Literacy, Culture, and International Education Division, GSE
Ezekiel Dixon-Román, Associate Professor, SP2
Julie Fairman, Nightingale Professor in Nursing; Chair, Biobehavioral Health Sciences Department; Director Emerita, Barbara Bates Center for the Study of the History of Nursing; Co-Director, RWJF Future of Nursing Scholars Program, Nursing
Kelly Jordan-Sciutto, Chair and Professor of Pathology, SDM
Carolina Lopez, Associate Professor of Microbiology and Immunology, Vet
Michael McGarvey, Associate Professor of Neurology at the Hospital of the University of Pennsylvania, PSOM
Katherine Milkman, Associate Professor of Operations, Information and Decisions, Wharton
Eve Troutt Powell, Christopher H. Browne Distinguished Professor of History and Associate Dean for Graduate Studies, SAS
Santosh Venkatesh, Professor of Electrical and Systems Engineering, SEAS, and Chair-Elect, Faculty Senate
Melissa Wilde, Associate Professor of Sociology, SAS
Christopher Yoo, John H. Chestnut Professor of Law, Communication, and Computer & Information Science, Law; Director, Center for Technology, Innovation & Competition, Law School
Kat McKay, C’17 (President of the Undergraduate Assembly)
Gaurav Shukla, student in the Master of Medical Physics Program, SAS (President of the Graduate and Professional Student Assembly)
Jane Xiao, C’17 (External Chair of the Student Committee on Undergraduate Education)
Fan (Alex) Yang, doctoral candidate, SEAS (Vice President of the Graduate and Professional Student Assembly)
Joann Mitchell, Senior Vice President for Institutional Affairs and Chief Diversity Officer
The search was supported by Adam P. Michaels, Deputy Chief of Staff in the President’s Office, and John Isaacson, John Muckle and Gregory Esposito of the executive search firm Isaacson, Miller.
The Committee and its consultants conducted informational interviews and consultative meetings with individuals and groups throughout the Penn community, as well as many informal contacts, in order to better understand the scope, expectations, and challenges of the Provost’s position and the opportunities facing the University in the years ahead. These consultative activities included full Committee meetings with Provost Vincent Price; Executive Vice President Craig Carnaroli; Vice Provosts Anita Allen, Dawn Bonnell, Ezekiel Emanuel, Valarie Ena Swain-Cade McCoullum, Carton Rogers, and Beth Winkelstein; Dean of Admissions Eric Furda; Director of the Division of Recreation and Intercollegiate Athletics M. Grace Calhoun; and Williams Director of the Penn Museum Julian Siggers. In addition, the Chair and the Committee members held open meetings for faculty and staff. The consultants interviewed administrators throughout the Provost’s Center and dozens of individuals and groups in the Penn community and sought nominations from presidents, provosts, and deans across the nation and the world as well as from leaders in government, foundations, academic societies and other organizations. Finally, members of the Committee engaged in extensive networking with Penn faculty and students, as well as colleagues at other institutions. The Committee also solicited advice and nominations from all Penn faculty, Deans, and senior administrators via email, and reviewed a variety of documents about the University.
Based upon these conversations and materials, the Committee’s charge from the President, and the Committee’s own discussions, a comprehensive document was prepared outlining the scope of the position and the challenges a new Provost will face, as well as the qualities sought in a new Provost. The vacancy was announced and input invited from the entire Penn community (Almanac January 10, 2016).
The Committee sought candidates with an uncompromising commitment to academic excellence, impeccable academic judgment, distinguished academic credentials and experience, and a steadfast and unwavering ethical compass. Candidates were asked to demonstrate a track record of achievement as an energetic, strong, and collaborative leader and administrator, providing evidence of a capacity to lead Penn’s academic enterprise in pursuit of the University’s highest priorities as articulated in Penn Compact 2020. The Committee sought evidence of candidates’ commitment to diversity in all its forms (i.e., racial, gender, socio-economic, intellectual, methodological, disciplinary, etc.). Evidence was also sought of success as an interdisciplinary thinker and to realizing Penn’s unique opportunities to advance the integration of knowledge through collaborative activities across traditional scholarly and institutional boundaries. Other key criteria included being a strategic, visionary and entrepreneurial leader with a proven ability to advance innovative understanding and discovery; a global outlook, with a strong commitment to leading efforts to strengthen Penn’s strategic engagement with local, national and international communities; an articulate, enthusiastic and effective communicator with the highest aspirations for Penn’s standing and reputation; and a commitment, ability and desire to broadly engage the University community, collaborate with the President, the Deans, and the faculty, staff and students, and function as a key member of the University’s senior management team.
Over the course of its four-month search process, the Committee and its consultants contacted and considered more than 160 individuals for the position. From these, the Committee selected 12 individuals for semi-finalist interviews with the entire Committee. Based on voluntary self-identifications and other sources, we believe the initial pool of 163 applicants, candidates, and nominees contained 56 women and 107 men, and 21 African-Americans and nine Latinos. The six individuals recommended for consideration to the President included one African-American and one woman and were selected from this group of 12 semi-finalists.
On April 26, 2017, President Gutmann announced the selection of Dr. Wendell Pritchett, Gr’97, as Provost. Dr. Pritchett is a celebrated teacher and scholar of urban policy, education, civil rights and race relations, an accomplished leader and administrator, and a passionate advocate for academic excellence and civic engagement. He assumed his office on July 1, 2017 after ratification by the Trustees at their June meeting.
—J. Larry Jameson, Chair of the Ad Hoc Consultative Committee for the Selection of a Provost
Ellen Neises: Executive Director of PennPraxis
Frederick Steiner, dean and Paley Professor at the University of Pennsylvania School of Design, has appointed Ellen Neises, GLA’02, to be the executive director of PennPraxis, the center for applied research, outreach and practice at the School. Ms. Neises is an adjunct associate professor in the department of landscape architecture at PennDesign and principal at RANGE, a landscape architecture and public policy practice.
Former director Randall Mason, associate professor of city and regional planning and chair of the Graduate Program in Historic Preservation, will remain active in the development of PennPraxis and its many projects as a senior fellow.
“Randy brought serious engagement with issues of equity and inclusion to our School, along with meaningful new research opportunities for students and faculty,” said Dean Steiner.
“I’m extremely proud of what PennPraxis has accomplished these past three years,” said Dr. Mason. “I look forward to working with Ellen as she expands PennPraxis’s advancement of social impact, collaborative practice and cutting-edge research.”
Ms. Neises said, “PennDesign is unique among art, design and planning schools to have a platform to demonstrate the power of design to solve problems and advance the kind of complex, community-engaged projects that I’m excited about—ones where we begin by helping define the opportunity, convene the right mix of creative thinkers to engage the ongoing debate, and generate options that are both strategic and imaginative. Through PennPraxis, faculty and students can collaborate on live projects that open up potentials for discussion and evaluation by multiple means and audiences, and we can translate ideas and community agendas shaped in this way, into strong prototypes and built places, research and policy solutions with big effects.”
Ms. Neises began as executive director on August 14, as PennPraxis launched A Year of Community-Engaged Design.
During Dr. Mason’s tenure, working in conjunction with managing director Julie Donofrio, PennPraxis strengthened its ties to Philadelphia institutions while expanding the organization’s reach globally. It published ambitious reports such as Civic Infrastructure: A Model for Civic Asset Reinvestment (funded by the William Penn Foundation), worked with numerous partners in the local Reimagining the Civic Commons initiative (funded by the Knight Foundation and William Penn Foundation, and organized by the Fairmount Park Conservancy), and a study of the inaugural Philly Free Streets event (with Open Streets PHL and the Knight Foundation). Praxis Dialogues convened policy makers, business leaders and community organizers in a series of public events to encourage debate on civic issues with national implications in partnership with PlanPhilly; student-led Social Impact Projects, funded by PennPraxis, supported PennDesign students’ work with area nonprofits like North Philly Peace Park, the Please Touch Museum, and Southeast by Southeast to strengthen communities directly. Internationally, Dr. Mason led a conservation and training project on genocide memorials in Rwanda, and helped launch faculty-led projects in Italy and Kuwait.
A PennDesign alumna and member of the faculty since 2011, Ms. Neises specializes in areas where both physical design and policy design are needed to advance major initiatives such as climate adaptation, sustainability of high-yield production agriculture, and quality of life and economic strength of industrial and environmental justice communities. Her firm, RANGE, and Philadelphia-based firm PORT Urbanism, were recently selected by the Regional Plan Association (RPA) to develop landscape infrastructure and design strategies for the 200-mile rural belt around the New York City metro area. With Richard Roark of OLIN, Ms. Neises led the PennDesign/OLIN team’s work on Hunts Point Lifelines, one of the six winning entries in the 2014 Rebuild by Design competition sponsored by the U.S. Department of Housing and Urban Development to develop contextual, scalable solutions to rebuild, protect and improve cities and towns hit by Hurricane Sandy. Her work in Pennsylvania includes an ongoing partnership with 10 municipalities and the Lehigh Valley Planning Commission to transform the 22-square mile Slate Belt through nature-based place making and economic development strategies.
Prior to coming to teach at Penn, Ms. Neises was an associate partner at James Corner Field Operations, where she helped build an international landscape architecture and urban design practice. Before earning a Master of Landscape Architecture from PennDesign in 2002, she worked for nine years on economic development, criminal justice and labor policy in New York, Alabama and Delaware. She holds a BS from Carnegie Mellon University and a Master of Public Policy from the Kennedy School of Government at Harvard.
PennPraxis will continue to be co-led by managing director Ms. Donofrio. Also a PennDesign alumna, Ms. Donofrio assumed her role in July of 2015 and has been instrumental in shaping the current mission-driven direction of PennPraxis, leading several of its Philadelphia-based projects, overseeing the student-generated Social Impact Projects, and guiding all programming and communications. Ms. Donofrio will continue this role, working in concert with Ms. Neises, managing office operations, local partnerships, and promoting engagement both within the School and with external partners.
Erin G. Cross: Director of the Lesbian Gay Bisexual Transgender Center
Erin G. Cross has been named director of the Lesbian Gay Bisexual Transgender (LGBT) Center at the University of Pennsylvania. Dr. Cross begins the new role September 13 upon the retirement of Robert Schoenberg, the Center’s inaugural director who spent 35 years serving and supporting Penn’s LGBTQ+ community. Dr. Cross has worked at the LGBT Center since 1998, most recently as the senior associate director.
Vice Provost for University Life Valarie Swain-Cade McCoullum said that Dr. Cross’ appointment “is the very embodiment of Penn President Amy Gutmann’s core tenets in Penn Compact 2020, as Dr. Cross will, with LGBT Center partners, continue to embrace its world-class mission: ‘To innovate, be radically inclusive and positively impact our local, national and global communities.’”
“I am thrilled to continue my career as director of the LGBT Center, my professional home,” Dr. Cross said. “Advising students, advocating for meaningful change, and building bridges across the Penn community have been, and will continue to be, my highest priorities. The LGBT Center is a welcoming space, a safe space, and an enduring space for all who enter.”
“I look forward to seeing Erin take on more leadership within a Center she helped build,” added Hikaru (Karu) Kozuma, associate vice provost for student affairs. “I am truly excited to work with her and continue the work to support the LGBT community at Penn.”
Dr. Cross also serves as a house fellow in Stouffer College House and a Pre-Major Advisor in the College of Arts and Sciences. She is a certified domestic violence/interpersonal violence advocate and an advisor for the Office of the Sexual Violence Investigative Officer.
At Penn, Dr. Cross has taught graduate-level classes on gender and sexuality in the Graduate School of Education. Her academic work includes serving as co-investigator on research projects including the Fels Institute’s Working Group on Policies Affecting LGBTQ Youth and Families and the Provost Office’s Inclusion of LGBTQ Students and Topics in Professional Education. She earned a PhD from Penn’s Graduate School of Education, a master’s in political science from Penn State University, and a bachelor’s in history and political science from the College of Wooster.