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

Peptide human leukocyte antigen (pHLA) targeting therapeutics like T-cell receptor 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 patien...

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Autores principales: Krämer, Stefan, Moritz, Andreas, Stehl, Luca, Hutt, Meike, Hofmann, Martin, Wagner, Claudia, Bunk, Sebastian, Maurer, Dominik, Roth, Günter, Wöhrle, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066226/
https://www.ncbi.nlm.nih.gov/pubmed/37002335
http://dx.doi.org/10.1038/s41598-023-32384-z
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author Krämer, Stefan
Moritz, Andreas
Stehl, Luca
Hutt, Meike
Hofmann, Martin
Wagner, Claudia
Bunk, Sebastian
Maurer, Dominik
Roth, Günter
Wöhrle, Johannes
author_facet Krämer, Stefan
Moritz, Andreas
Stehl, Luca
Hutt, Meike
Hofmann, Martin
Wagner, Claudia
Bunk, Sebastian
Maurer, Dominik
Roth, Günter
Wöhrle, Johannes
author_sort Krämer, Stefan
collection PubMed
description Peptide human leukocyte antigen (pHLA) targeting therapeutics like T-cell receptor 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 towards a large pHLA library. Compared to a dataset obtained by conventional bio-layer interferometry measurements, we illustrate that a massively increased throughput (over 650 fold) is obtained by our microarray screening, paving the way for use in pre-clinical safety screening of pHLA-targeting drugs.
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spelling pubmed-100662262023-04-02 An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions Krämer, Stefan Moritz, Andreas Stehl, Luca Hutt, Meike Hofmann, Martin Wagner, Claudia Bunk, Sebastian Maurer, Dominik Roth, Günter Wöhrle, Johannes Sci Rep Article Peptide human leukocyte antigen (pHLA) targeting therapeutics like T-cell receptor 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 towards a large pHLA library. Compared to a dataset obtained by conventional bio-layer interferometry measurements, we illustrate that a massively increased throughput (over 650 fold) is obtained by our microarray screening, paving the way for use in pre-clinical safety screening of pHLA-targeting drugs. Nature Publishing Group UK 2023-03-31 /pmc/articles/PMC10066226/ /pubmed/37002335 http://dx.doi.org/10.1038/s41598-023-32384-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Krämer, Stefan
Moritz, Andreas
Stehl, Luca
Hutt, Meike
Hofmann, Martin
Wagner, Claudia
Bunk, Sebastian
Maurer, Dominik
Roth, Günter
Wöhrle, Johannes
An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title_full An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title_fullStr An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title_full_unstemmed An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title_short An ultra-high-throughput screen for the evaluation of peptide HLA-Binder interactions
title_sort ultra-high-throughput screen for the evaluation of peptide hla-binder interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066226/
https://www.ncbi.nlm.nih.gov/pubmed/37002335
http://dx.doi.org/10.1038/s41598-023-32384-z
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