CAR-T cell therapy for cancer: current challenges and future directions
Abstract Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid l...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02269-w |
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| author | Inés Zugasti Lady Espinosa-Aroca Klaudyna Fidyt Vladimir Mulens-Arias Marina Diaz-Beya Manel Juan Álvaro Urbano-Ispizua Jordi Esteve Talia Velasco-Hernandez Pablo Menéndez |
| author_facet | Inés Zugasti Lady Espinosa-Aroca Klaudyna Fidyt Vladimir Mulens-Arias Marina Diaz-Beya Manel Juan Álvaro Urbano-Ispizua Jordi Esteve Talia Velasco-Hernandez Pablo Menéndez |
| author_sort | Inés Zugasti |
| collection | DOAJ |
| description | Abstract Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid leukemia (AML), the most common acute leukemia in adults and the elderly. Simultaneously, CAR-T cell therapies continue to face significant challenges in the treatment of solid tumors. The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effective and safe, as AML cells share most surface antigens with healthy hematopoietic stem and progenitor cells (HSPCs). Simultaneously targeting antigen expression on both AML cells and HSPCs may result in life-threatening on-target/off-tumor toxicities such as prolonged myeloablation. In addition, the immunosuppressive nature of the AML tumor microenvironment has a detrimental effect on the immune response. This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical application. It then explores the current landscape of CAR-T cell therapy in both hematologic malignancies and solid tumors. Finally, the review delves into the specific challenges of applying CAR-T cell therapy to AML, highlights ongoing global clinical trials, and outlines potential future directions for developing effective CAR-T cell-based treatments for relapsed/refractory AML. |
| format | Article |
| id | doaj-art-b2dc49cba1534357a54bb2f44bcde932 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-b2dc49cba1534357a54bb2f44bcde9322025-08-20T03:45:41ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-0110115110.1038/s41392-025-02269-wCAR-T cell therapy for cancer: current challenges and future directionsInés Zugasti0Lady Espinosa-Aroca1Klaudyna Fidyt2Vladimir Mulens-Arias3Marina Diaz-Beya4Manel Juan5Álvaro Urbano-Ispizua6Jordi Esteve7Talia Velasco-Hernandez8Pablo Menéndez9Hematology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Josep Carreras Leukemia Research InstituteJosep Carreras Leukemia Research InstituteJosep Carreras Leukemia Research InstituteHematology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Red Española de Terapias Avanzadas (TERAV), Instituto de Salud Carlos IIIHematology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Hematology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Josep Carreras Leukemia Research InstituteJosep Carreras Leukemia Research InstituteAbstract Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid leukemia (AML), the most common acute leukemia in adults and the elderly. Simultaneously, CAR-T cell therapies continue to face significant challenges in the treatment of solid tumors. The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effective and safe, as AML cells share most surface antigens with healthy hematopoietic stem and progenitor cells (HSPCs). Simultaneously targeting antigen expression on both AML cells and HSPCs may result in life-threatening on-target/off-tumor toxicities such as prolonged myeloablation. In addition, the immunosuppressive nature of the AML tumor microenvironment has a detrimental effect on the immune response. This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical application. It then explores the current landscape of CAR-T cell therapy in both hematologic malignancies and solid tumors. Finally, the review delves into the specific challenges of applying CAR-T cell therapy to AML, highlights ongoing global clinical trials, and outlines potential future directions for developing effective CAR-T cell-based treatments for relapsed/refractory AML.https://doi.org/10.1038/s41392-025-02269-w |
| spellingShingle | Inés Zugasti Lady Espinosa-Aroca Klaudyna Fidyt Vladimir Mulens-Arias Marina Diaz-Beya Manel Juan Álvaro Urbano-Ispizua Jordi Esteve Talia Velasco-Hernandez Pablo Menéndez CAR-T cell therapy for cancer: current challenges and future directions Signal Transduction and Targeted Therapy |
| title | CAR-T cell therapy for cancer: current challenges and future directions |
| title_full | CAR-T cell therapy for cancer: current challenges and future directions |
| title_fullStr | CAR-T cell therapy for cancer: current challenges and future directions |
| title_full_unstemmed | CAR-T cell therapy for cancer: current challenges and future directions |
| title_short | CAR-T cell therapy for cancer: current challenges and future directions |
| title_sort | car t cell therapy for cancer current challenges and future directions |
| url | https://doi.org/10.1038/s41392-025-02269-w |
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