Scientific Symposium Gets to ‘Heart of Disease’ With Cell and Gene Therapy Talks

The 17th Research Institute Scientific Symposium, held virtually on May 20, highlighted advances in cell and gene therapy.

limjr [at] chop.edu (By Jillian Rose Lim)

Going virtual couldn’t stop the spirit of scientific inquiry at the 17^th annual Research Institute Scientific Symposium, held May 20 as a BlueJeans event. Close to 200 participants from Children’s Hospital of Philadelphia and the University of Pennsylvania community logged in from homes, offices, and labs for the highly anticipated event, “back on track for many years to come,” as Bryan Wolf, MD, PhD, Executive Vice President and Chief Scientific Officer (CSO), said in his opening remarks.

The event featured a stellar lineup of speakers divided into four sessions surrounding the theme, “Advances in Cell and Gene Therapy.” Dr. Wolf kick-started the event by saying the Research Institute will be “in great hands” with Susan Furth, MD, PhD, his successor as CSO starting June 1.

“I hope I can carry on [Dr. Wolf’s] spirit of energy and support for moving CHOP forward and catalyzing our impact on child health across the world,” said Dr. Furth, currently Vice Chair in the Department of Pediatrics.

Passing the CSO Baton

Already a familiar face among her Research Institute and Penn colleagues, Dr. Furth began her opening remarks with the significance of the symposium to her new position.

“This [event] embodies two of the things that are the most important to me as I assume this role,” Dr. Furth said. “One, promoting discovery that can translate to therapies that improve the health and outcomes of children; and two, the training and development and mentoring of scientists, researchers, and investigators that will propel our work forward and embody the values that we have in our mission on child health.”

Dr. Furth described cell and gene therapy as one of CHOP’s most “forefront and impactful programs” and shared some insights on the field’s significance. Quoting a book penned by Barton Childs, MD, a past mentor at Johns Hopkins University, Dr. Furth shared Dr. Child’s notion that in the future, all medicine or therapy would be based on the individuality of the gene-environment interaction.

“[Dr. Childs] had some poetic words that ‘the gene is at the heart of disease, and DNA provides a language that prefigures possibilities and constraints for both the development and the present of the homeostasis of cells,’” Dr. Furth said. “I think since the time he wrote that to now, our understanding has proliferated and enabled the kind of breakthroughs that we’ll describe today. By working in this arena and leading gene therapies that originated at CHOP and Penn, we are providing enormous impact in the field going forward.”

Cell and Gene Therapy Across CHOP

A CHOP investigator chaired each of the symposium’s four sessions — Gene Therapy, Cell Therapy for Cancer, Emerging Approaches, and Translating Gene Therapies. Lindsey George, MD, assistant professor of Pediatrics, led the first session on Gene Therapy.

The section included talks from Alejandro Mas Monteys, PhD, assistant professor in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Maxwell Chapwell, PhD student in the Division of Hematology, and Megan Keiser, PhD, research scientist in the Department of Pathology and Laboratory Medicine. The presenters discussed drug-related splicing switches for gene expression control, gene therapy approaches for alpha thalassemia (a disorder affecting the production of normal hemoglobin), and the translation of gene therapies for spinocerebellar ataxia type 1 (a neurodegenerative disease).

Next, Stephan Grupp, MD, PhD, director of Translational Research in the Center for Childhood Cancer Research, chaired the session on Cell Therapy for Cancer. Presenters included Jan Joseph Melenhorst, PhD, research professor in Pathology and Lab Medicine, Gregory Chen, MD, PhD, student in the Division of Oncology, Jessica Foster, MD, physician in Oncology, and Guillem Pascual-Pasto, PhD, postdoctoral fellow in Oncology. The presenters described insights into tracking the fate of chimeric antigen receptor (CAR) T-cells, factors mediating the long-term persistence of CAR T-cell therapy, the development of mRNA CAR T cells for malignant pediatric brain tumors, and the dual targeting of pediatric solid tumors through CAR T cells.

The third session chaired by Beverly Davidson, PhD, Chief Scientific Strategy Officer and Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, focused on emerging approaches for cell and gene therapies. Presenters included William Peranteau, MD, surgeon in the Division of General, Thoracic and Fetal Surgery, Zhiwei Ang, PhD, postdoctoral fellow in Pathology and Lab Medicine, Anna Sternberg, PhD, postdoctoral fellow in Hematology, Lucas Tricoli, PhD, research associate in Hematology, and Mark Yarmarkovich, PhD, postdoctoral fellow in Oncology.

Finally, Stefano Rivella, PhD, investigator in Hematology, chaired the fourth session on the translation of gene therapies. Presenters included Janet Kwiatkowski, MD, MSCE, physician in Hematology, Ellie Carrell, PhD, postdoctoral fellow in Pathology and Lab Medicine, and Denise Sabatino, PhD, investigator in Hematology. Participants learned about LentiGlobin gene therapy for beta thalassemia, combined transgene and intron-derived miRNA therapy, and the genetic consequences of AAV-mediated gene correction.

Keynote: Gene Editing for Blood Disorders

After a break, invited guest Daniel Bauer, MD, PhD, an associate professor of Pediatrics at Harvard Medical School, provided the keynote for the symposium. Also the director of the Gene Therapy Program and a Hematology staff physician at Boston Children’s Hospital, Dr. Bauer’s work has translated remarkably from mechanistic studies to the clinic. His research focuses on functional genomics to dissect determinants of blood cell development and disease to develop innovative therapies. As Dr. George mentioned in her keynote introduction, Dr. Bauer’s seminal 2013 Science paper outlined the role of the BCL11A erythroid enhancer in fetal hemoglobin regulation, paving the way for potential therapeutic application for β-hemoglobinopathies (disorders caused by mutations in the β-globin gene). His lab continues to study the molecular mechanisms of hemoglobin switching and various advanced gene editing approaches.

During his talk, “Gene Editing for Blood Disorders,” Dr. Bauer spoke about gene editing for hemoglobin disorders, including the preclinical work conducted by himself and colleagues, and the subsequent factors and challenges involved in clinical implication. In the second part of his lecture, Dr. Bauer discussed his work on gene editing to explore therapeutic opportunities for autosomal dominant disease. In autosomal dominant disease, a single copy of the disease-associated mutation is sufficient to cause disease. Dr. Bauer delved into a number of studies that provide proof of principle that he hopes lead to much simpler therapies.

By the end of the symposium, it was clear the virtual format didn’t dampen curiosity and opportunities for collaboration: The audience continuously filled the Q&A chat function with an abundance of questions, comments, ideas, and insights.

In her closing remarks, Dr. Davidson thanked the presenters and co-organizers of the event, including the Office of Academic Training and Outreach Programs, and Dr. Grupp for conceiving this year’s focus on advances in cell and gene therapy; it was the second year that the symposium had a devoted theme. 

“The first [thematic symposium] was on big data, the second on cell and gene therapy, and the third — who knows,” Dr. Davidson said. “So if you have ideas, please submit them to me and Dr. Furth, and we’re happy to consider those for future years.”