An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions

An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions Stefan Krämer, Andreas Moritz, Luca Stehl, Meike Hutt, Martin Hofmann, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2499422/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Mar, 2023 Read the published version in Scientific Reports → Version 1 posted 8 You are reading this latest preprint version Abstract Peptide-HLA (pHLA) targeting therapeutics like TCR-based adoptive cell therapy or bispecific T cell engaging receptor molecules hold great promise for the treatment of cancer. Comprehensive pre-clinical screening of therapeutic candidates is important to ensure patient safety but is challenging because of the size of the potential off-target space. By combining stabilized peptide-receptive HLA molecules with microarray printing and screening, we have developed an ultra-high-throughput screening platform named ValidaTe that enables large scale evaluation of pHLA-binder interactions. We demonstrate its potential by measuring and analyzing over 30.000 binding curves for a high-affinity T cell Engaging Receptor (TCER) towards a large pHLA library. Compared to a dataset obtained by conventional bio-layer interferometry (BLI) measurements, we illustrate that a massively increased throughput is obtained by our microarray screening without compromises in data quality, paving the way for use in pre-clinical safety screening of pHLA-targeting drugs. Biological sciences/Immunology/Immunotherapy Biological sciences/Drug discovery/Drug safety Biological sciences/Drug discovery/Drug screening/High throughput screening Biological sciences/Biological techniques/High throughput screening Biological sciences/Biological techniques/Sensors and probes Full Text Additional Declarations Competing interest reported. S.K., L.S., G.R. and J.W. are employees of BioCopy GmbH. The described method is commercially available as a service provided by BioCopy GmbH. S.K., G.R. and J.W. are inventors of the method for generation of complex arrays patented by BioCopy GmbH. A.M., M.Hutt, M.Hofmann, C.W., S.B., D.M. were employees of Immatics in the course of this work and may have securities from Immatics. Supplementary Files SupplementDataS1.xlsx Cite Share Download PDF Status: Published Journal Publication published 31 Mar, 2023 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Major revision 02 Mar, 2023 Reviews received at journal 19 Feb, 2023 Reviewers agreed at journal 15 Feb, 2023 Reviewers invited by journal 15 Feb, 2023 Editor assigned by journal 24 Jan, 2023 Editor invited by journal 24 Jan, 2023 Submission checks completed at journal 24 Jan, 2023 First submitted to journal 20 Jan, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2499422","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":170237055,"identity":"78433c9d-3062-4e69-8c1f-a092c8a8caff","order_by":0,"name":"Stefan 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