Autor: |
Stefan Krämer, Andreas Moritz, Luca Stehl, Meike Hutt, Martin Hofmann, Claudia Wagner, Sebastian Bunk, Dominik Maurer, Günter Roth, Johannes Wöhrle |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Scientific Reports, Vol 13, Iss 1, Pp 1-8 (2023) |
Druh dokumentu: |
article |
ISSN: |
2045-2322 |
DOI: |
10.1038/s41598-023-32384-z |
Popis: |
Abstract 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. |
Databáze: |
Directory of Open Access Journals |
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