Artículo
Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies
Autor/es | García Calderón, Clara Beatriz
Sierro-Martínez, Belén García-Guerrero, Estefanía Sanoja-Flores, Luzalba Muñoz-García, Raquel Ruiz-Maldonado, Victoria Carrasco-Brocal, Inmaculada Pérez Simón, José Antonio Caballero Velázquez, Teresa |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2023 |
Fecha de depósito | 2024-02-08 |
Publicado en |
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Resumen | 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. ... 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. |
Agencias financiadoras | "Plan de Recuperacion Transformacion y Resiliencia" and Consejeria de Salud y Familia, Junta de Andalucia, CSYF 2021 - Proyectos Fondos FEDER Instituto de Salud Carlos III (ISCIII) Red Espanola de Terapias Avanzadas TERAV - European Union-NextGenerationEU |
Identificador del proyecto | PECART-0185-2020-7
PECART-0185-2020 RD21/0017/0021 |
Cita | 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. |
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