Scott, Jamie I.Mendive Tapia, LorenaGordon, DoireannBarth, Nicole D.Thompson, Emily J.Cheng, ZhimingTaggart, DavidKitamura, TakanoriBravo-Blas, AlbertoRoberts, Edward W.Juárez Jiménez, JordiMichel, JulienPiet, BerberVries, I. Jolanda deVerdoes, MartijnDawson, JohnCarragher, NeilO' Connor, Richard A.Akram, Ahsan R.Frame, MargaretSerrels, AlanVendrell, Marc2022-09-282022-09-282022-05-022041-1723https://hdl.handle.net/2445/189387Immunotherapy 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.application/pdfengcc-by (c) Scott, Jamie I. et al., 2022https://creativecommons.org/licenses/by/4.0/CàncerPèptidsSíntesi orgànicaCancerPeptidesOrganic synthesisinfo:eu-repo/semantics/article7243342022-09-28info:eu-repo/semantics/openAccess