dc.creator | García Calderón, Clara Beatriz | es |
dc.creator | Sierro-Martínez, Belén | es |
dc.creator | García-Guerrero, Estefanía | es |
dc.creator | Sanoja-Flores, Luzalba | es |
dc.creator | Muñoz-García, Raquel | es |
dc.creator | Ruiz-Maldonado, Victoria | es |
dc.creator | Carrasco-Brocal, Inmaculada | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.creator | Caballero Velázquez, Teresa | es |
dc.date.accessioned | 2024-02-08T11:31:34Z | |
dc.date.available | 2024-02-08T11:31:34Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | García Calderón, C.B., Sierro-Martínez, B., García-Guerrero, E., Sanoja-Flores, L., Muñoz-García, R., Ruiz-Maldonado, V.,...,Caballero Velázquez, T. (2023). Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies. Frontiers in Immunology, 14 (1152498). https://doi.org/10.3389/fimmu.2023.1152498. | |
dc.identifier.issn | 1664-3224 | es |
dc.identifier.uri | https://hdl.handle.net/11441/154921 | |
dc.description.abstract | Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes.
Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed.
Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control.
Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy. | es |
dc.format | application/pdf | es |
dc.format.extent | 15 p. | es |
dc.language.iso | eng | es |
dc.publisher | Frontiers Media | es |
dc.relation.ispartof | Frontiers in Immunology, 14 (1152498). | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B-ALL | es |
dc.subject | CAR-T | es |
dc.subject | Lymphoma | es |
dc.subject | Biomarkers | es |
dc.subject | DPCR (digital PCR) | es |
dc.subject | Flow cytometry | es |
dc.subject | Monitoring | es |
dc.title | Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.projectID | PECART-0185-2020-7 | es |
dc.relation.projectID | PECART-0185-2020 | es |
dc.relation.projectID | RD21/0017/0021 | es |
dc.relation.publisherversion | https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1152498/full | es |
dc.identifier.doi | 10.3389/fimmu.2023.1152498 | es |
dc.journaltitle | Frontiers in Immunology | es |
dc.publication.volumen | 14 | es |
dc.publication.issue | 1152498 | es |
dc.contributor.funder | "Plan de Recuperacion Transformacion y Resiliencia" and Consejeria de Salud y Familia, Junta de Andalucia, CSYF 2021 - Proyectos Fondos FEDER | es |
dc.contributor.funder | Instituto de Salud Carlos III (ISCIII) | es |
dc.contributor.funder | Red Espanola de Terapias Avanzadas TERAV - European Union-NextGenerationEU | es |