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2022-05-02

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cc-by (c) Scott, Jamie I. et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/189387

A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies

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https://doi.org/10.1038/s41467-022-29691-w

Resum

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.

Matèries

Càncer, Pèptids, Síntesi orgànica

Matèries (anglès)

Cancer, Peptides, Organic synthesis

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Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

Citació

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. A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies. _Nature Communications_. 2022. Vol. 13, núm. 2366. [consulta: 29 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/189387]

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