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García-Calderón, Clara Beatriz; Sierro-Martínez, Belén; García-Guerrero, Estefanía; Sanoja-Flores, Luzalba; Muñoz-García, Raquel; Ruiz-Maldonado, Victoria; Jimenez-Leon, María Reyes; Delgado-Serrano, Javier; Molinos-Quintana, Águeda; Guijarro-Albaladejo, Beatriz; Carrasco-Brocal, Inmaculada; Lucena, José-Manuel; García-Lozano, José-Raúl; Blázquez-Goñi, Cristina; Reguera-Ortega, Juan Luis; González-Escribano, María-Francisca; Reinoso-Segura, Marta; Briones, Javier; Pérez-Simón, José Antonio; Caballero-Velázquez, Teresa

Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies

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  • Medientyp: E-Artikel
  • Titel: Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies
  • Beteiligte: García-Calderón, Clara Beatriz; Sierro-Martínez, Belén; García-Guerrero, Estefanía; Sanoja-Flores, Luzalba; Muñoz-García, Raquel; Ruiz-Maldonado, Victoria; Jimenez-Leon, María Reyes; Delgado-Serrano, Javier; Molinos-Quintana, Águeda; Guijarro-Albaladejo, Beatriz; Carrasco-Brocal, Inmaculada; Lucena, José-Manuel; García-Lozano, José-Raúl; Blázquez-Goñi, Cristina; Reguera-Ortega, Juan Luis; González-Escribano, María-Francisca; Reinoso-Segura, Marta; Briones, Javier; Pérez-Simón, José Antonio; Caballero-Velázquez, Teresa
  • Erschienen: Frontiers Media SA, 2023
  • Erschienen in: Frontiers in Immunology
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fimmu.2023.1152498
  • ISSN: 1664-3224
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Purpose</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Experimental design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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. </jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang