The U.S. Food and Drug Administration (FDA) approved a game-changing cellular therapy in August 2017 to treat cancer with a patient’s own immune system. Kymriah™, the first therapy based on gene transfer to be approved by the agency, targets patients age 25 and under who are battling an aggressive blood cancer known as B-cell precursor acute lymphoblastic leukemia (ALL).

Developed by CHOP and the University of Pennsylvania in partnership with Novartis, Kymriah is a chimeric antigen receptor (CAR) T-cell therapy that modifies patients’ own immune T cells. The modified cells are collected and reprogrammed at a Novartis facility and then infused back into the patients’ bodies to seek and destroy the leukemia cells.

In 2012, CHOP became the first institution to investigate how CAR T-cell therapy could be used to treat pediatric patients who have ALL. While ALL is the most common childhood cancer, an effective treatment has been elusive.

Updated results from a global clinical trial of the CAR T-cell therapy, also known as tisagenlecleucel, reveal that children and young adults continued to show high rates of durable, complete remission of their disease. Most side effects were short-lived and reversible, according to a study published in the New England Journal of Medicine.

“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” said lead author Shannon L. Maude, MD, PhD, a pediatric oncologist at CHOP and assistant professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. “Our data show not only can we can achieve longer-term durable remissions, and longer-term survival for our patients, but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job.”

In the “Inspiration” section of this Annual report, read the story of 9-year-old Austin Schuetz, a Cub Scout, collector, and cancer survivor from Wisconsin who participated in early clinical trials at CHOP for the treatment.

CHOP and The Wistar Institute celebrated the 10th anniversary of a vaccine against rotavirus, a major worldwide killer of children under age 5. Rotavirus is a widespread microbe that infects the gastrointestinal system, causing severe diarrhea and vomiting, which can be life-threatening in young children.

Research conducted by CHOP and Wistar scientists starting in the 1980s culminated in FDA approval of the Rotateq® vaccine in 2006. Before Rotateq, approximately half a million children ended up in the emergency room with rotavirus every year, with 75,000 hospitalized with severe dehydration. Up to 60 children hospitalized died each year. Thanks to Rotateq, today, child hospitalizations from rotavirus have dropped by 85 percent in the U.S. The vaccine is also saving children’s lives around the world.

CHOP’s Partners for Child Passenger Safety (PCPS) program, the nation’s first large-scale child-focused crash surveillance system, turned 20 in 2017. In its first 10 years of existence, PCPS conducted the world’s largest research project focused on children in motor vehicle accidents, studying more than 875,000 children involved in 600,000 crashes, conducting 33,000 interviews, and analyzing over 800 on-site investigations.

Created in collaboration with State Farm Insurance, PCPS used its study findings to make recommendations about child safety that have shaped and advanced the future of vehicle design, legislation, and public health education. Most importantly, PCPS has contributed to reducing the number of children dying in automobile crashes each year from more than 2,000 in the 1990s to approximately 1,000 in 2017. PCPS also has helped save many more children from serious injury.

CHOP’s Center for Autism Research took part in the Infant Brain Imaging Study network, which discovered a brain biomarker that may help identify children with autism spectrum disorder (ASD) earlier in life with the help of a computer-generated algorithm. The findings seem to confirm what researchers have long suspected — that changes in the brain may precede behavioral manifestations of ASD.

Autism is typically diagnosed in children around age 4 in the U.S., but by that time, their brains have already changed substantially and tend to be enlarged. Increased brain size was one of the earliest brain markers discovered in autism, which is characterized by difficulties in social interaction, verbal and nonverbal communication, repetitive behaviors, and restricted interests.

Previously, brain size had only been studied in children and adults after the full onset of autism. The study findings could result in diagnosing a child with autism much earlier, before the full onset of symptoms. The ability to intervene as early as a child’s first year of life could offer the potential to mitigate the development of autism and improve long-term outcomes.

A rare genetic growth condition was named after the three scientists at CHOP who extensively studied and defined it as a recognizable disorder. Mulchandani-Bhoj-Conlin Syndrome (MBCS) is characterized by mild prenatal growth deficiency, slow growth, and the lack of desire to eat.

MBCS takes its name from Surabhi Mulchandani, MS, genetic counselor and manager of the Genomic Diagnostics Laboratory; Elizabeth Bhoj, MD, PhD, clinician-researcher in the Division of Human Genetics; and Laura Conlin, PhD, director in the Genomic Diagnostics Laboratory. In defining the characteristics of MBCS, including the unusual chromosomal pattern, the three scientists conducted 13,000 genetic tests over eight years and published a research article on their findings.

Normally, children inherit one copy of each chromosome from each parent, but children with MBCS receive both copies of chromosome 20 from their mother only. Researchers don’t know yet what causes the absence of paternally inherited genes on chromosome 20.

But the recognition of a clear, definable disorder with an official name brings hope to families. The CHOP scientists found that children treated with growth hormones put them back on track developmentally, and none experienced long-term delays. It also brings clarity for physicians because many conditions cause babies to have trouble gaining weight.

The U.S. Food and Drug Administration landmark approval of Luxturna™ marked the nation’s first gene therapy approved for the treatment of a genetic disease, and it was the culmination of more than a decade of dedication and perseverance by the CHOP-Penn-Spark research team and the commitment of the patients and families who participated in the clinical studies.

“The FDA’s approval of Luxturna highlights the vital role of pediatric research in developing breakthrough cures,” stated Bryan Wolf, MD, PhD, Executive Vice President and Chief Scientific Officer of CHOP Research Institute. “Spanning the course of 10 years, the research conducted at CHOP’s Center for Cellular and Molecular Therapeutics laid the groundwork for this revolutionary gene therapy.”

The one-time gene therapy product is indicated for the treatment of patients with a rare, inherited form of retinal blindness called biallelic RPE65 mutation-associated retinal dystrophy. An estimated 1,000 to 2,000 patients in the U.S. with RPE65 mutations experience visual impairment at infancy or early childhood and become totally blind by mid-life. The therapy delivers corrected versions of the RPE65 gene in a single injection using a genetically engineered, benign adeno-associated virus to carry the genes to the retina.

Spark Therapeutics, a Philadelphia biotechnology company created in 2013 by CHOP to accelerate the timeline for bringing new gene therapies to market, led the late-stage clinical development of the therapy. Spark was built on the foundational research conducted at CHOP’s Raymond G. Perelman Center for Cellular and Molecular Therapeutics under the direction of then-CHOP-researcher Katherine High, MD, a gene therapy pioneer who is now Spark’s president and head of research and development.

The initial research also was spearheaded by Jean Bennett, MD, PhD, F.M. Kirby professor of Ophthalmology at the Perelman School of Medicine at the University of Pennsylvania’s Scheie Eye Institute, and Albert Maguire, MD, a professor of Ophthalmology at Penn Medicine and an attending physician at CHOP, who served as a principal investigator of the therapy’s clinical trials.