a83e6364980e74eb464e509b0acde589 303462.pdf febee8128b0b5972d63ac770bea9b775abe4b151 303462.pdf ac1df7bfb6284509253f0377892cf03cdc628a74a262b51aa652aa45195f336c 303462.pdf Title: Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies Subject: 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. Keywords: CAR-T, flow cytometry, dPCR (digital PCR), monitoring, biomarkers, B-ALL, Lymphoma Author: Clara Beatriz García-Calderón CreationDate: Mon Apr 10 05:49:16 2023 CEST ModDate: Mon Apr 10 06:33:16 2023 CEST Custom Metadata: no Metadata Stream: yes Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.389 x 841.663 pts (A4) Page rot: 0 File size: 4406834 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HGIOCD+AdvTTd3a5f740 Type 1C WinAnsi yes yes no 671 0 HGIODD+AdvTTd3a5f740+01 Type 1C MacRoman yes yes no 672 0 HGIODE+AdvPSA18C Type 1C WinAnsi yes yes no 673 0 HGIODF+AdvTTd3a5f740+20 Type 1C WinAnsi yes yes no 674 0 HGIODG+AdvTT9b12cd41 Type 1C WinAnsi yes yes no 681 0 HGIODH+AdvTT9b12cd41+01 Type 1C MacRoman yes yes no 682 0 HGIODI+AdvPSA323 Type 1C WinAnsi yes yes no 683 0 HGIODJ+AdvTT9b12cd41+fb Type 1C Custom yes yes yes 684 0 HGIODK+AdvTT2c8ce45a Type 1C WinAnsi yes yes no 685 0 HGJBCJ+AdvTT9b12cd41+20 Type 1C WinAnsi yes yes no 695 0 HGJBCK+AdvTTd168d80a.I Type 1C WinAnsi yes yes no 697 0 HGJBGK+AdvTT2c8ce45a+fb Type 1C Custom yes yes yes 377 0 HGJBGL+AdvOT1ef757c0 Type 1C WinAnsi yes yes no 393 0 HGJBGM+AdvOT1ef757c0+fb Type 1C Custom yes yes yes 386 0 HGJBGN+AdvOT7d6df7ab.I Type 1C WinAnsi yes yes no 383 0 HGJBGO+AdvOT1ef757c0+20 Type 1C WinAnsi yes yes no 380 0 HGJBHO+AdvTT749c1f5a.I Type 1C WinAnsi yes yes no 375 0 HGJBHP+AdvTTd3a5f740+fb Type 1C Custom yes yes yes 390 0 HGJBKA+AdvOT1ef757c0+01 Type 1C MacRoman yes yes no 395 0 HGJBKB+AdvTT58d178b9+03 Type 1C Custom yes yes yes 403 0 HGJBKC+AdvOTd877c31c Type 1C WinAnsi yes yes no 400 0 HGJBKD+AdvOTd877c31c+21 Type 1C WinAnsi yes yes no 397 0 HGJBKE+AdvOT1ef757c0+22 Type 1C Custom yes yes yes 396 0 HGJBLE+AdvOT3f84ef53 Type 1C WinAnsi yes yes no 406 0 HGJKHP+HelveticaNeueLTStd-Bd Type 1C WinAnsi yes yes no 409 0 HGJLPH+AdvOT46dcae81 Type 1C WinAnsi yes yes no 412 0 HGMBBE+AdvTT02dee1cd.I+03 Type 1C Custom yes yes yes 413 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-28 02:47:38 CET RepresentationInformation: 303462.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-27 12:58:17 CET Size: 4406834 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 755 FreeObjects: 1 IncrementalUpdates: 2 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies Destination: bmark_1939609504 Children: Item: Title: 1 Introduction Destination: s1 Item: Title: 2 Materials and methods Destination: s2 Children: Item: Title: 2.1 Ex vivo PBMCs isolation and manufacturing of academic CD19 CAR-T’cells Destination: s2_1 Item: Title: 2.2 Patient samples Destination: s2_2 Item: Title: 2.3 Flow cytometry Destination: s2_3 Item: Title: 2.4 Digital PCR Destination: s2_4 Item: Title: 2.5 Data analysis Destination: s2_5 Item: Title: 3 Results Destination: s3 Children: Item: Title: 3.1 Validation of flow cytometric CD19 CAR staining with different reagents Destination: s3_1 Item: Title: 3.2 CAR-T cell kinetics and phenotype characterization Destination: s3_2 Item: Title: 3.3 Correlation of CAR-T cell expansion in vivo with toxicity and event-free survival Destination: s3_3 Item: Title: 3.4 Increased exhaustion markers at peak expansion correlate with increased event-free survival Destination: s3_4 Item: Title: 4 Discussion Destination: s4 Item: Title: Data availability statement Destination: s5 Item: Title: Ethics statement Destination: s6 Item: Title: Author contributions Destination: s7 Item: Title: Funding Destination: bmark_1865464027 Item: Title: Supplementary material Destination: bmark_632582120 Item: Title: References Destination: bmark_2090415954 Info: Title: Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies Author: Clara Beatriz García-Calderón Subject: 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. 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José-Raúl García-Lozano Cristina Blázquez-Goñi Juan Luis Reguera-Ortega María-Francisca González-Escribano Marta Reinoso-Segura Javier Briones José Antonio Pérez-Simón Teresa Caballero-Velázquez 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. Copyright © 2023 García-Calderón, Sierro-Martínez, García-Guerrero, Sanoja-Flores, Muñoz-García, Ruiz-Maldonado, Jimenez-Leon, Delgado-Serrano, Molinos-Quintana, Guijarro-Albaladejo, Carrasco-Brocal, Lucena, García-Lozano, Blázquez-Goñi, Reguera-Ortega, González-Escribano, Reinoso-Segura, Briones, Pérez-Simón and Caballero-Velázquez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies CAR-T flow cytometry dPCR (digital PCR) monitoring biomarkers B-ALL Lymphoma CAR-T, flow cytometry, dPCR (digital PCR), monitoring, biomarkers, B-ALL, Lymphoma True https://www.frontiersin.org/legal/copyright-statement 2023-04-10T12:33:16+08:00 2023-04-10T11:49:16+08:00 2023-04-10T12:33:16+08:00 uuid:d03a427f-142e-4d2e-809d-75d2042527ed uuid:aa95512d-f0d2-4c47-b234-87dc55397c4f Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 222, 641, 476, 662 Annotation: Subtype: Link Rect: 222, 616, 443, 637 Annotation: Subtype: Link Rect: 222, 591, 522, 612 Annotation: Subtype: Link Rect: 222, 566, 497, 587 Annotation: Subtype: Link Rect: 222, 541, 459, 562 Annotation: Subtype: Link Rect: 49, 33, 129, 40 Annotation: Subtype: Link Rect: 500, 33, 545, 40 Annotation: Subtype: Link Rect: 49, 646, 125, 661 Annotation: Subtype: Link Rect: 60, 493, 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