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http://hdl.handle.net/2445/189387
Title: | A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies |
Author: | Scott, Jamie I. Mendive Tapia, Lorena Gordon, Doireann Barth, Nicole D. Thompson, Emily J. Cheng, Zhiming Taggart, David Kitamura, Takanori Bravo-Blas, Alberto Roberts, Edward W. Juárez Jiménez, Jordi Michel, Julien Piet, Berber Vries, I. Jolanda de Verdoes, Martijn Dawson, John Carragher, Neil O' Connor, Richard A. Akram, Ahsan R. Frame, Margaret Serrels, Alan Vendrell, Marc |
Keywords: | Càncer Pèptids Síntesi orgànica Cancer Peptides Organic synthesis |
Issue Date: | 2-May-2022 |
Publisher: | Nature Publishing Group |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-29691-w |
It is part of: | Nature Communications, 2022, vol. 13, num. 2366 |
URI: | http://hdl.handle.net/2445/189387 |
Related resource: | https://doi.org/10.1038/s41467-022-29691-w |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica) |
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