{"doi":"10.1172/jci171396","title":"BCMA- and CST6-specific CAR T cells lyse multiple myeloma cells and suppress murine osteolytic lesions","abstract":"We have previously demonstrated that cystatin E/M (CST6), which is elevated in a subset of patients with multiple myeloma (MM) lacking osteolytic lesions (OLs), suppresses MM bone disease by blocking osteoclast differentiation and function. CST6 is a secreted type 2 cystatin, a cysteine protease inhibitor that regulates lysosomal cysteine proteases and the asparaginyl endopeptidase legumain. Here, we developed B cell maturation antigen (BCMA) CST6 chimeric antigen receptor T cells (CAR-T cells), which lysed MM cells and released CST6 proteins. Our in vitro studies show that these CAR-T cells suppressed the differentiation and formation of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Using xenografted MM mice, bioluminescence images showed that both BCMA-CAR-T and BCMA-CST6-CAR-T cells inhibited MM growth to a similar extent. Reconstructed micro-computed tomography images revealed that BCMA-CST6-CAR-T cells, but not BCMA-CAR-T cells, prevented MM-induced bone damage and decreased osteoclast numbers. Our results provide a CAR-T strategy that targets tumor cells directly and delivers an inhibitor of bone resorption.","journal":"Journal of Clinical Investigation","year":2023,"id":364742,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":736309,"name":"Yan Cheng","orcid":"0000-0001-7877-9622","position":1,"is_corresponding":false},{"id":422716,"name":"Jin‐Ran Chen","orcid":"0000-0001-6984-5878","position":2,"is_corresponding":false},{"id":233671,"name":"Visanu Wanchai","orcid":"0000-0003-2243-3838","position":3,"is_corresponding":false},{"id":514616,"name":"David E. Mery","orcid":"0000-0002-8327-9777","position":4,"is_corresponding":false},{"id":1035962,"name":"Hongwei Xu","orcid":"0000-0002-0470-705X","position":5,"is_corresponding":false},{"id":697602,"name":"Dongzheng Gai","orcid":null,"position":6,"is_corresponding":false},{"id":753884,"name":"Samer Al Hadidi","orcid":"0000-0003-4297-8042","position":7,"is_corresponding":false},{"id":469850,"name":"Carolina Schinke","orcid":"0000-0002-2699-1741","position":8,"is_corresponding":false},{"id":469854,"name":"Sharmilan Thanendrarajan","orcid":"0000-0003-2593-411X","position":9,"is_corresponding":false},{"id":61733,"name":"Maurizio Zangari","orcid":"0000-0002-1720-3854","position":10,"is_corresponding":false},{"id":61737,"name":"Frits van Rhee","orcid":"0000-0001-9959-1282","position":11,"is_corresponding":false},{"id":61740,"name":"Guido Tricot","orcid":"0000-0002-3111-9739","position":12,"is_corresponding":false},{"id":61745,"name":"John D. Shaughnessy","orcid":"0000-0002-2017-6236","position":13,"is_corresponding":false},{"id":61726,"name":"Fenghuang Zhan","orcid":"0000-0001-6208-1676","position":14,"is_corresponding":false},{"id":437921,"name":"Fumou Sun","orcid":"0000-0003-2034-3492","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T01:14:41.218128Z","pmid":"37883186","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":[]}