Allergies, Delivery Modes, and Feeding Methods; Genomic Profiling; Tagging CAR T Cells; ‘and the Award Goes to …’

By Nancy McCann

It may feel like winter arrived in the city this week, but that doesn’t mean our scientists have gone into hibernation. Quite the opposite, actually. This week’s research roundup includes a story in Newsweek covering intriguing results of an allergy study presented at a national conference, and Cell Reports covers research that could serve as a resource for pediatric cancer drug development. You’ll also learn how researchers at Children’s Hospital of Philadelphia and the University of Pennsylvania have discovered a new way to track CAR T cells in the body, and who, among our deserving investigators, received a prestigious science award for providing inspiration and determination in building an outstanding home for research.

Newsweek Covers Allergy Research by World-renowned CHOP Doc

CHOP allergist, David Hill, MD, PhD, and co-author of the study “How a Baby is Delivered and How They Feed Can Affect Allergy Onset,” presented the intriguing results at the American College of Allergy, Asthma, and Immunology Annual Scientific Meeting in Houston, earlier this month. 

Investigating how the allergic march may be influenced by birthing and feeding methods (vaginally vs. C-section, and breastfed vs. formula-fed), the research team studied medical charts of 158,422 children who were seen at CHOP over the past 20 years. The children fell into one of five categories: allergy-free, or had either eczema, a food allergy, asthma, or hay fever. The study revealed the children who were delivered vaginally were less likely to have allergies than children who weren’t. It also showed those who were exclusively or partially breastfed were less likely to develop an allergy.

“There have been prior studies that have suggested links between environmental factors and allergic outcomes,” Dr. Hill told Newsweek. “Some of these factors are thought to influence the makeup of commensal bacteria that live in harmony on our skin and in our digestive tract. Delivery mode and feeding practices are two examples of such environmental factors.”

Read the story online, the printed version in the Nov. 18, 2019, issue of Newsweek, or this news brief for more information.

Finding a Way to Accelerate Cures for Children With Cancer 

Preclinical testing of new therapeutic anti-cancer agents is essential in the field of pediatric oncology due to the relative rarity of the condition and the need to prioritize agents for early-phase clinical trials. 

A study published this month in Cell Reports by corresponding author, John Maris, MD, who holds the Giulio D’Angio Chair in Neuroblastoma Research, sheds light on how to systematically prioritize and rationally test new drugs by genomic profiling of childhood tumor patient-derived xenograft (PDX) models.  

Dr. Maris and the research team, led by bioinformatics scientist Jo Lynne Rokita, PhD, and in collaboration with the Pediatric Preclinical Testing Consortium (PPTC), defined the genetic landscape of PDX models of 37 unique pediatric cancers and demonstrated that they faithfully recapitulate the genetic landscape of these cancers in patients and made all of the data and models freely available to the research community Alex’s Lemonade Stand Foundation funded this work.   

“We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer,” Dr. Maris said.

Tagging CAR T Cells With Imaging Markers to Monitor Cancer Therapy in Body

With CAR T-cell therapy, a patient’s own immune cells are genetically modified and inserted back into the body to find and kill cancer. This form of immunotherapy has already revolutionized some cancer treatments, but once the CAR T cells are inside a patient, where do they go? How do doctors know that they have successfully reached their target and that they are continuing to fight disease weeks, months, or even years later?

Researchers have discovered a new way to track CAR T cells in the body, according to a study co-led by Sarah Richman MD, PhD, an attending physician at CHOP, and scientists in the Perelman School of Medicine at Penn. The researchers genetically engineered CAR T cells with molecular tags, which they were able to monitor in an animal model using position emission tomography (PET) imaging. The results appeared in the journal Molecular Therapy.

“Currently, the only way to know whether a gene or cell therapy is still present in the body is to regularly biopsy tumors or draw blood, which offer very crude measurements of the therapy. With our technology, clinicians would be able to see, quantitatively, the number and location of CAR T cells that have lasted in the body over time, which is an indicator of the therapy’s durability and potential efficacy,” said co-author Mark Sellmyer, MD, PhD, assistant professor of Radiology at Penn. “Imaging CAR T cells also will allow researchers to more easily test and modify therapies for many different types of disease in the research setting.”

Learn more in Penn Medicine News.

Paul Offit, MD, Honored With Prestigious Science Award

A big shoutout goes to Children’s Hospital of Philadelphia doc Paul Offit, MD, director of the Vaccine Education Center (VEC) and an internationally recognized expert in the fields of virology and immunology. He’s the recipient of the distinguished Geoffrey Beene Foundation Builders of Science Award from Research!America which recognizes those who have provided inspiration and determination in building an outstanding home for research.

“There are those of us who, like me, grew up with polio, mumps, and measles – and saw the ravages of those diseases in children,” Dr. Offit said. “Sadly, we’re seeing children succumb to these vaccine preventable diseases all over again. It is incumbent on all of us to know the truth, defend the truth, and communicate the truth about vaccines: They save lives.” 

Dr. Offit, will receive the award at the March 2020 Research!America advocacy awards event in Washington, D.C., which brings together leaders from government, industry, academia, patient groups, scientific societies, independent research institutes, and health advocacy organizations to honor exceptional advocates for research. 

See CHOP News for more information. Read Penn Today for Dr. Offit’s five tips for better communicating tough scientific topics. 

Patterns of Spinal Curvature in Children May Predict Scoliosis in Teens

Saba Pasha, PhD, MS, director of Orthopaedic Engineering and 3D Musculoskeletal Imaging Research Program at CHOP, has identified patterns of spinal curvature in younger children that may be likely to develop into scoliosis by adolescence. 

Accurately predicting scoliosis, a common, abnormal curvature of the spine, could set the stage for the first-ever methods to prevent the potentially disabling condition. These are significant findings, considering pediatric scoliosis is the most common spinal deformity worldwide — affecting close to 4 percent of children.

Using X-rays of 129 adolescents — with and without scoliosis — Dr. Pasha applied computer analysis and simulations to investigate how elastic rods, modeling children’s spines, change shape in response to mechanical loading. 

“This was the first study to quantitatively explain how variation in spinal patterns may lead to the spinal deformities seen in scoliosis, and may eventually guide us to early interventions for children at risk,” said Dr. Pasha, who is also on the faculty of the Perelman School of Medicine at Penn.

See CHOP News for more details of Dr. Pasha’s novel findings. Read Dr. Pasha’s study online in Nature Scientific Reports.

ICYMI

Catch up on our headlines from our last edition of In the News:

• Clinic Helps Parents Encourage Kids to Eat Varied Foods
• Research Fellow Kshitiz Singh Receives Career Development Award
• Genomics Research Network Expands With New NIH Grant
• Improving Medication Adherence for Children With Asthma 

That’s it for this briefing! Keep up with our news, stories, and updates in real time by following us on Twitter, Facebook, LinkedIn, or Instagram. Or subscribe to our newsletter to get an email sent every other Friday by signing up here, or via the box on the upper right of this page.