Newswise — The winner of the Columbia Softball Pediatric Award, Peter Madsen, MD, presented his research, In Silico Identification of Neo-Antigens in a High-Grade Pediatric Brain Tumor Cohort Utilizing Next-Generation Sequencing: Pilot Study of a Discovery Pipeline for Immunotherapy Targets, during the 2018 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.
High-grade pediatric brain tumors include a variety of histopathologic entities, but as a group may be more likely to benefit from immunotherapies, given their frequent lack of targetable driver mutations, underlying epigenetic abnormalities and often hyper-mutated status. To that end, study authors present preliminary results from a computational pipeline that seeks to identify potential tumor-specific antigens for targeted immunotherapy development.
Advances in computational biology have made it possible to test tumor-specific novel peptides against an HLA-specific MHC receptor in silico to identify binding epitopes that may illicit a host response or be the foundation for tumor vaccines or adoptive immunotherapies. Pediatric patients with high-grade brain tumor pathologies, for which next-generation sequencing data was available, were identified and subjected to a modified version of this established computational pipeline. Filtered results of this affinity test were considered to be potential tumor neo-antigens.
A cohort of 46 patients were identified, which included 17 patients with high-grade glioma, 15 with DIPG, 12 with medulloblastoma and two with ATRT. Tumor samples had, on average, 17 mutations that lead to the generation of novel tumor-specific peptides. When assessed for MHC binding interaction, this yielded an average of 66 candidate neo-antigens per sample with a range of 2-347 candidates. Authors identified 19 genes generating conserved candidate neo-antigens that were shared among at least two samples. Some recurrent candidate neo-antigens noted for further exploration included the product of the H3F3A K27M mutation (found in 13 samples) as well as conserved mutations in SLC9B1 (found in four samples), PLIN4 (found in three samples) and ZNF705A (found in three samples).
In this pilot study, authors identified potential recurrent tumor neo-antigens across multiple patient samples and histopathological disease types in a small cohort of high-grade pediatric brain tumor patients. Further work is needed to validate this in silico technique and translate the results into new immunotherapies.
This work comes from The Center for Data Driven Discovery in Biomedicine (D3b), a translational, convergent biomedicine research center at Children’s Hospital of Philadelphia that combines domain expertise across disciplines to accelerate the bench-to-bedside research cycle on behalf of children. The Center’s underpinnings are based on newly emergent convergence research principles and underpinned by large-scale, integrated data initiatives for translation to clinical impact.
Author Block: Bo Zhang; Katherine Wang; Angela Waanders, MD, MPH; Phillip Storm, MD; Adam Resnick, PhD
Disclosure: The author reported no conflicts of interest.
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About the 2018 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals, the AANS Annual Scientific Meeting is the largest gathering of neurosurgeons in the nation, with an emphasis on the field’s latest research and technological advances. The scientific presentations accepted for the 2018 event will represent cutting-edge examples of the incredible developments taking place within the field of neurosurgery. Find additional information about the 2018 AANS Annual Scientific Meeting and the meeting program here.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 11,000 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. Fellows of the AANS are board-certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons of Canada or the Mexican Council of Neurological Surgery, A.C. Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the spinal column, spinal cord, brain, nervous system and peripheral nerves.
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2018 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting