{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fang C"],"funding":["Shenzhen Medical Research Fund","Shenzhen Natural Science Fund","Chinese National Major Project for New Drug Innovation","Shenzhen Science and Technology Foundation","National Natural Science Foundation of China","Shenzhen Clinical Research Center for hematologic disease","Sanming Project of Medicine in Shenzhen","Shenzhen Key Laboratory","HaiYa Young Scientist Foundation of Shenzhen University General Hospital","Natural Science Foundation of Shenzhen University General Hospital"],"pagination":["1251"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12604393"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(1)"],"pubmed_abstract":["Background
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) disease. B-cell maturation antigen (BCMA)-targeted CAR-T therapy, exemplified by FDA-approved agents like ide-cel and cilta-cel, offers promise, yet accessibility barriers necessitate local production.Methods
This single-arm trial evaluated safety/efficacy of autologous BCMA CAR-T cells in six R/R MM patients.Results
Cytokine release syndrome (CRS) occurred in 83% (grade 1), managed with tocilizumab without neurotoxicity. Toxicities were transient and resolved. Serum cytokine (IFN-γ, IL-6/8/10) peaked during CRS. Responses included 83% overall response (67% stringent complete response), unaffected by extramedullary disease or high-risk cytogenetics. Median PFS/OS were unreached, with an estimated 12-month OS rate of 83.33% and PFS rate of 66.67%. CAR-T cell persistence, with a median Cmax at 20.5 days, remained detectable in 83% at 1 month and 67% at 6 months. Single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing (TCR-seq) demonstrated complementary roles of functionally specialized CD8⁺ Te subsets. Clonal evolution in the sustained responder (patient 2) revealed a shift from a polyclonal infusion product (IP) to oligoclonal dominance, with shared clones exhibiting enhanced cytotoxic and NK-like activity. Transcriptional adaptation of persistent clones over time indicated distinct phases of proliferation, stress response, and long-term persistence, with a concomitant shift in cellular phenotype from IP-derived Tem/circling T cells to a mixed Tem/Te_1/Te_2 population. Comparative analysis of two patients with divergent clinical outcomes (sustained remission vs. transient remission) revealed that early CAR-T exhaustion and increased regulatory T cells (Tregs) were associated with relapse.Conclusions
Locally produced BCMA CAR-T is safe and effective in heavily pretreated R/R MM, inducing deep responses. scRNA-seq/TCR-seq findings highlight interplay of CAR-T heterogeneity, clonal adaptability, and immune regulation. CD8⁺ subset specialization and clonal persistence matter for durable responses; exhaustion and immunosuppression may cause relapse."],"journal":["Journal of translational medicine"],"pubmed_title":["Integrated clinical and single-cell profiling of BCMA CAR-T therapy in relapsed/refractory multiple myeloma."],"pmcid":["PMC12604393"],"funding_grant_id":["82030076, 82070161, 81970151, 81670162 and 81870134","ZDSYS20200811143757022","JCYJ20190808163601776, JCYJ20200109113810154","SZSM202111004","C2301003","2019ZX09201002003","SUGH2019QD012","LCYSSQ20220823091401002","20200830182623001","HY002"],"pubmed_authors":["Tan K","Yu L","Guo X","Zhao W","Fang C","Wang H","Meng X","Wang L","Li Y","Chen Z","He Z","Yu C","Huang W","Wang S","Mei J","Wang Y","Qiao J","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Integrated clinical and single-cell profiling of BCMA CAR-T therapy in relapsed/refractory multiple myeloma.","description":"Background
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) disease. B-cell maturation antigen (BCMA)-targeted CAR-T therapy, exemplified by FDA-approved agents like ide-cel and cilta-cel, offers promise, yet accessibility barriers necessitate local production.Methods
This single-arm trial evaluated safety/efficacy of autologous BCMA CAR-T cells in six R/R MM patients.Results
Cytokine release syndrome (CRS) occurred in 83% (grade 1), managed with tocilizumab without neurotoxicity. Toxicities were transient and resolved. Serum cytokine (IFN-γ, IL-6/8/10) peaked during CRS. Responses included 83% overall response (67% stringent complete response), unaffected by extramedullary disease or high-risk cytogenetics. Median PFS/OS were unreached, with an estimated 12-month OS rate of 83.33% and PFS rate of 66.67%. CAR-T cell persistence, with a median Cmax at 20.5 days, remained detectable in 83% at 1 month and 67% at 6 months. Single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing (TCR-seq) demonstrated complementary roles of functionally specialized CD8⁺ Te subsets. Clonal evolution in the sustained responder (patient 2) revealed a shift from a polyclonal infusion product (IP) to oligoclonal dominance, with shared clones exhibiting enhanced cytotoxic and NK-like activity. Transcriptional adaptation of persistent clones over time indicated distinct phases of proliferation, stress response, and long-term persistence, with a concomitant shift in cellular phenotype from IP-derived Tem/circling T cells to a mixed Tem/Te_1/Te_2 population. Comparative analysis of two patients with divergent clinical outcomes (sustained remission vs. transient remission) revealed that early CAR-T exhaustion and increased regulatory T cells (Tregs) were associated with relapse.Conclusions
Locally produced BCMA CAR-T is safe and effective in heavily pretreated R/R MM, inducing deep responses. scRNA-seq/TCR-seq findings highlight interplay of CAR-T heterogeneity, clonal adaptability, and immune regulation. CD8⁺ subset specialization and clonal persistence matter for durable responses; exhaustion and immunosuppression may cause relapse.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T15:06:39.043Z","creation":"2026-05-18T03:12:56.872Z"},"accession":"S-EPMC12604393","cross_references":{"pubmed":["41214679"],"doi":["10.1186/s12967-025-07106-w"]}}