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

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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.

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Nature Communications, 2022, vol. 13, num. 2366

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

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