{"doi":"10.1021/jacs.5c04392","title":"Granzyme B-Targeting Quenched Activity-Based Probes for Assessing Tumor Response to Immunotherapy","abstract":"High Resolution Image Download MS PowerPoint Slide Molecular imaging of immune activation holds tremendous potential for the development of novel immunotherapies. In particular, chemical probes capable of detecting immune responses before changes in tumor size occur can guide early therapeutic strategies. Here, we present a quenched activity-based probe targeting granzyme B as a biomarker of antitumor immunity. Through optimization of the peptide recognition element and functional chemical warhead, we have developed an optical imaging probe, Cy5-IEPCya PhP -QSY21, which rapidly reacts with granzyme B at substoichiometric concentrations and enables efficient, selective labeling of the active enzyme in a complex proteome. With high specificity and minimal background signal, this probe produces granzyme B-induced near-infrared fluorescence signals in the tumors of living mice shortly after injection. Both in vivo and ex vivo fluorescence signals correlate with granzyme B expression and activity, and the population of CD8+ cells in tumor tissues. Moreover, it demonstrates the potential to track tumor response to immunotherapy. Thus, this study offers a chemical tool for assessing immune-mediated anticancer activity using noninvasive optical imaging.","journal":"Journal of the American Chemical Society","year":2025,"id":520185,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":903543,"name":"Arghya Ganguly","orcid":null,"position":1,"is_corresponding":false},{"id":1390181,"name":"Sebastian M. Malespini","orcid":null,"position":2,"is_corresponding":false},{"id":952906,"name":"Lai Thang","orcid":null,"position":3,"is_corresponding":false},{"id":283916,"name":"Nimit L. Patel","orcid":"0000-0002-8251-7155","position":4,"is_corresponding":false},{"id":816773,"name":"Caleb Kim","orcid":null,"position":5,"is_corresponding":false},{"id":1259977,"name":"Kalyani Thakur","orcid":"0000-0001-8856-3278","position":6,"is_corresponding":false},{"id":428818,"name":"Joseph D. Kalen","orcid":"0000-0002-7163-4604","position":7,"is_corresponding":false},{"id":106855,"name":"Claudia Calcagno","orcid":"0000-0002-4325-8728","position":8,"is_corresponding":false},{"id":439423,"name":"Simone Difilippantonio","orcid":"0000-0002-8234-1559","position":9,"is_corresponding":false},{"id":582286,"name":"Euna Yoo","orcid":"0000-0001-5982-1979","position":10,"is_corresponding":false},{"id":1389755,"name":"Muhammad Kazim","orcid":"0000-0003-2020-8952","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:49:28.470782Z","pmid":"41061668","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}