The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes1. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies2,3. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks4. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A 24:02, which is derived from the neuroblastoma-dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (PC-CARs) through a counter panning strategy using predicted potentially cross-reactive peptides. We further proposed th
Scientists have been trying to identify every gene in the human genome since the initial draft was published in 2001. In the years since, much progress has been made in identifying protein-coding genes, currently estimated to number fewer than 20,000, with an ever-expanding number of distinct protein-coding isoforms. Here we review the status of the human gene catalogue and the efforts to complete it in recent years. Beside the ongoing annotation of protein-coding genes, their isoforms and pseudogenes, the invention of high-throughput RNA sequencing and other technological breakthroughs have led to a rapid growth in the number of reported non-coding RNA genes. For most of these non-coding RNAs, the functional relevance is currently unclear; we look at recent advances that offer paths forward to identifying their functions and towards eventually completing the human gene catalogue. Finally, we examine the need for a universal annotation standard that includes all medically significant g
A Better Telescope Gazing at the Transcriptome genengnews.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from genengnews.com Daily Mail and Mail on Sunday newspapers.
Tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained,
clinically meaningful reductions in asthma exacerbations in individuals with severe,
uncontrolled asthma. These findings are consistent with previous randomised, placebo-controlled
studies and show the long-term safety and sustained efficacy of tezepelumab in individuals
with severe, uncontrolled asthma.
In a surprise move this year, the university recognizes two faculty members with the full award; each will receive $250,000 to support their groundbreaking research