Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia

Leukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients’ T cells to target and destroy resistant cancer cells. This study re...

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Main Authors: Elżbieta Bartoszewska, Maciej Tota, Monika Kisielewska, Izabela Skowron, Kamil Sebastianka, Oliwia Stefaniak, Klaudia Molik, Jakub Rubin, Karolina Kraska, Anna Choromańska
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/18/1596
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author Elżbieta Bartoszewska
Maciej Tota
Monika Kisielewska
Izabela Skowron
Kamil Sebastianka
Oliwia Stefaniak
Klaudia Molik
Jakub Rubin
Karolina Kraska
Anna Choromańska
author_facet Elżbieta Bartoszewska
Maciej Tota
Monika Kisielewska
Izabela Skowron
Kamil Sebastianka
Oliwia Stefaniak
Klaudia Molik
Jakub Rubin
Karolina Kraska
Anna Choromańska
author_sort Elżbieta Bartoszewska
collection DOAJ
description Leukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients’ T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.
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publisher MDPI AG
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series Cells
spelling doaj-art-b256e547e1084f96962743432fc0c8b72025-08-20T01:55:22ZengMDPI AGCells2073-44092024-09-011318159610.3390/cells13181596Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for LeukemiaElżbieta Bartoszewska0Maciej Tota1Monika Kisielewska2Izabela Skowron3Kamil Sebastianka4Oliwia Stefaniak5Klaudia Molik6Jakub Rubin7Karolina Kraska8Anna Choromańska9Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandFaculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandLeukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients’ T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.https://www.mdpi.com/2073-4409/13/18/1596leukemiapediatric oncologyCAR-T therapyacute lymphoblastic leukemiaacute myeloid leukemiaantigen escape
spellingShingle Elżbieta Bartoszewska
Maciej Tota
Monika Kisielewska
Izabela Skowron
Kamil Sebastianka
Oliwia Stefaniak
Klaudia Molik
Jakub Rubin
Karolina Kraska
Anna Choromańska
Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
Cells
leukemia
pediatric oncology
CAR-T therapy
acute lymphoblastic leukemia
acute myeloid leukemia
antigen escape
title Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
title_full Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
title_fullStr Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
title_full_unstemmed Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
title_short Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia
title_sort overcoming antigen escape and t cell exhaustion in car t therapy for leukemia
topic leukemia
pediatric oncology
CAR-T therapy
acute lymphoblastic leukemia
acute myeloid leukemia
antigen escape
url https://www.mdpi.com/2073-4409/13/18/1596
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