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http://hdl.handle.net/2445/189387
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DC Field | Value | Language |
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dc.contributor.author | Scott, Jamie I. | - |
dc.contributor.author | Mendive Tapia, Lorena | - |
dc.contributor.author | Gordon, Doireann | - |
dc.contributor.author | Barth, Nicole D. | - |
dc.contributor.author | Thompson, Emily J. | - |
dc.contributor.author | Cheng, Zhiming | - |
dc.contributor.author | Taggart, David | - |
dc.contributor.author | Kitamura, Takanori | - |
dc.contributor.author | Bravo-Blas, Alberto | - |
dc.contributor.author | Roberts, Edward W. | - |
dc.contributor.author | Juárez Jiménez, Jordi | - |
dc.contributor.author | Michel, Julien | - |
dc.contributor.author | Piet, Berber | - |
dc.contributor.author | Vries, I. Jolanda de | - |
dc.contributor.author | Verdoes, Martijn | - |
dc.contributor.author | Dawson, John | - |
dc.contributor.author | Carragher, Neil | - |
dc.contributor.author | O' Connor, Richard A. | - |
dc.contributor.author | Akram, Ahsan R. | - |
dc.contributor.author | Frame, Margaret | - |
dc.contributor.author | Serrels, Alan | - |
dc.contributor.author | Vendrell, Marc | - |
dc.date.accessioned | 2022-09-28T07:16:44Z | - |
dc.date.available | 2022-09-28T07:16:44Z | - |
dc.date.issued | 2022-05-02 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/2445/189387 | - |
dc.description.abstract | Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B. We demonstrate that probe H5 enables the real-time detection of T cell-mediated anticancer activity in mouse tumors and in tumors from lung cancer patients. Furthermore, we show image-based phenotypic screens, which reveal that the AKT kinase inhibitor AZD5363 shows immune-mediated anticancer activity. The reactivity of probe H5 may enable the monitoring of early responses to anticancer treatments using tissue biopsies. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-29691-w | - |
dc.relation.ispartof | Nature Communications, 2022, vol. 13, num. 2366 | - |
dc.relation.uri | https://doi.org/10.1038/s41467-022-29691-w | - |
dc.rights | cc-by (c) Scott, Jamie I. et al., 2022 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Pèptids | - |
dc.subject.classification | Síntesi orgànica | - |
dc.subject.other | Cancer | - |
dc.subject.other | Peptides | - |
dc.subject.other | Organic synthesis | - |
dc.title | A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 724334 | - |
dc.date.updated | 2022-09-28T07:16:45Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/771443/EU//DYNAFLUORS | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/859908/EU//NOVA-MRI | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/957535/EU//IBDIMAGE | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica) |
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724334.pdf | 2.68 MB | Adobe PDF | View/Open |
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