CHOP Cell and Gene Therapy Experts Elected to National Academy of Medicine

By Jillian Rose Lim

On the heels of major breakthroughs in gene therapy — and amidst ongoing discoveries to come — Beverly Davidson, PhD, and Stephan Grupp, MD, PhD, were elected into the National Academy of Medicine (NAM), one of the nation’s most prestigious medical organizations. Both Dr. Davidson, who is director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children’s Hospital of Philadelphia, and Dr. Grupp, director of the Cancer Immunotherapy Program at CHOP, have pioneered the development of innovative therapies for hard-to-treat and often fatal conditions — changing the lives of patients across the world.  

“CHOP has the brightest minds in cellular and gene therapy under one roof, coupled with unparalleled experience with the first-to-market approved gene therapies, and our unique infrastructure that makes it possible to deliver these therapies,” said Bryan Wolf, MD, PhD, executive vice president and chief scientific officer, in a CHOP press release. “All of this powers our pediatric research hospital to aggressively pursue and lead treatment breakthroughs. Dr. Davidson’s and Dr. Grupp’s elections to the National Academy of Medicine are very well deserved.”

Two Decades of Discovery and Counting

For Dr. Davidson, the milestone is a culmination of more than 20 years of work taking advantage of technologies to create new genetic medicines for brain disorders and solving difficult problems in neurology. 

“It’s terrific to be nominated for consideration into the Academy, which is a recognition of one’s life’s work and those contributions to the broader medical field,” said Dr. Davidson, who is also chief scientific strategy officer at CHOP. “But I’m even more proud to have been elected into the National Academy of Medicine.” 

Her work thus far has focused on expanding our understanding of the molecular basis of neurodegeneration in inherited genetic diseases affecting the central nervous system (CNS) and developing novel molecular medicines. Now, as one of the newest members of the NAM, Dr. Davidson hopes to bring these situations around gene therapy into the national forum. 

“How do we advance these therapies for ultra rare disorders outside of the competitive space?” Dr. Davidson asked. “How do we collaborate and integrate with the National Institutes of Health and the U.S. Food and Drug Administration to really move [sic] these genetic medicines for the kids and adults who need them?” 

These are just some of the questions Dr. Davidson has explored and will continue to pursue as a member of the NAM. But while her research at CHOP and Penn can continually be defined as cutting-edge and innovative, the motivation behind Dr. Davidson’s work has steadfastly remained the same since graduate school:

“I’ve always straddled the translational interface between basic research into inherited brain disorders, and then thinking about how we can capitalize on what we discover in the basic arena to advance therapies for diseases that affect the CNS,” Dr. Davidson said. “And as we learn more about what’s going on in patients suffering from these disorders, new opportunities arise to intervene using a variety of modalities.”

Notably, Dr. Davidson’s team developed and applied novel methods of delivering therapeutic genes to the CNS. Earlier this year, she led a study published in Nature Communications that advanced the use of adeno-associated viral (AAV) vectors, a clinical tool for gene editing pioneered at CHOP, by reporting a novel screening method for better detecting sites where the vectors deliver genetic cargo in the body. Among other discoveries, Dr. Davidson’s lab also pioneered the design of gene-lowering technologies for the treatment of dominant disorders such as Huntington’s disease and spinocerebellar ataxias, using RNA interference and gene-editing technologies.

Leading the Field of Cancer Immunotherapy

For Dr. Grupp, who is also chief of the Cell Therapy and Transplant Section in the Division of Oncology at CHOP, the NAM election comes at an exciting and rapidly advancing time in gene therapy. Dr. Grupp was recognized for his pivotal work in developing a novel type of cancer immunotherapy for acute lymphoblastic leukemia (ALL), one of the most common cancers in children but also one of the most aggressive. The innovative treatment, known as chimeric antigen receptor T-cell therapy, or CTL019 CAR T, was the first-ever gene therapy for cancer and has saved the lives of many children and young adults with relapsed and refractory ALL. Dr. Grupp’s status as a leader in cancer immunotherapy has been recognized both at home and around the world.

“It is an incredible honor to take a seat at this table at the time cellular and gene therapies are advancing to the fore,” said Dr. Grupp in a CHOP press release. “New fields of medicine are being invented in front of our eyes. For children with fatal cancers, the urgency has always been there. Now, we can truly accelerate cures. From successfully treating our first patient with incurable acute lymphoblastic leukemia, Emily Whitehead, with CAR T, to the first-ever U.S. Food and Drug Administration approval of the CAR T therapy CTL019 (tisagenlecleucel) in five short years, is an unprecedented trajectory. It is an amazing opportunity to join this distinguished group of clinicians and researchers to coach, cheer, and continue to push hard to advance these new approaches.”

Collaborating with Carl June, MD, director of the Center for Cellular Immunotherapies at the University of Pennsylvania, and his team, Dr. Grupp led many preclinical in vivo studies of CTL019 before pioneering clinical trials for CTL019 in pediatric patients with an advanced form of ALL. Before this, Dr. Grupp and his research lab had been devoted to developing molecularly targeted and cell-based therapies to treat leukemia and solid tumors for over two decades — alongside treating patients in his role as an oncologist specializing in aggressive neuroblastoma. 

“There are few among us who know the tremendous time commitment, bravery, and unwavering belief in better outcomes for children it requires to do what he has done,” said  Joseph W. St. Geme, MD, physician-in-chief and chairman of the Department of Pediatrics at CHOP, in a press release. “We echo the sentiment of his colleagues, our families, and young patients given another chance at life in saying he is highly deserving of this recognition.”

The NAM election means Drs. Davidson and Grupp will continue to move full speed ahead with their science.

“To have been elected makes me very proud of the work my lab has done and the contributions that we’ve made in the past,” Dr. Davidson said. “And we’re not done yet. We hope to continue to advance our discoveries into therapies for individuals suffering from disorders that affect the brain. It makes me very proud to represent CHOP in the bigger picture, as I work with other Academy members to focus on the topics that will have an impact and are of interest broadly to this field.”