Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma
Abstract: Relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy remains a major challenge in B-cell acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (B-NHL). One of the main strategies to avoid CD19-negative relapse has been the development of dual CAR T cells...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924007006 |
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| author | Gustavo de Oliveira Canedo Claire Roddie Persis J. Amrolia |
| author_facet | Gustavo de Oliveira Canedo Claire Roddie Persis J. Amrolia |
| author_sort | Gustavo de Oliveira Canedo |
| collection | DOAJ |
| description | Abstract: Relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy remains a major challenge in B-cell acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (B-NHL). One of the main strategies to avoid CD19-negative relapse has been the development of dual CAR T cells targeting CD19 and an additional target, such as CD22 or CD20. Different methods have been used to achieve this, including coadministration of 2 products targeting 1 single antigen, cotransduction of autologous T cells, use of a bicistronic vector, or the development of bivalent CARs. Phase 1 and 2 trials across all manufacturing strategies have shown this to be a safe approach with equivalent remission rates and initial product expansion. CAR T-cell persistence remains a significant issue, with the majority of relapses being antigen-positive after CAR T-cell infusion. Further, despite adding a second antigen, antigen-negative relapses have not yet been eliminated. This review summarizes the state of the art with dual-targeting CAR T cells for B-cell ALL and B-NHL, the challenges encountered, and possible next steps to overcome them. |
| format | Article |
| id | doaj-art-afd0985a0a434a43bb5d641552302188 |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-afd0985a0a434a43bb5d6415523021882025-02-12T05:31:37ZengElsevierBlood Advances2473-95292025-02-0194704721Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphomaGustavo de Oliveira Canedo0Claire Roddie1Persis J. Amrolia2Molecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, United KingdomDepartment of Haematology, University College London Hospitals, London, United KingdomMolecular and Cellular Immunology Section, University College London Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, United Kingdom; Correspondence: Persis J. Amrolia, Molecular and Cellular Immunology Section, Great Ormond Street Institute of Child Health, 20c Guilford St, London WC1N 1DZ, United Kingdom;Abstract: Relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy remains a major challenge in B-cell acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (B-NHL). One of the main strategies to avoid CD19-negative relapse has been the development of dual CAR T cells targeting CD19 and an additional target, such as CD22 or CD20. Different methods have been used to achieve this, including coadministration of 2 products targeting 1 single antigen, cotransduction of autologous T cells, use of a bicistronic vector, or the development of bivalent CARs. Phase 1 and 2 trials across all manufacturing strategies have shown this to be a safe approach with equivalent remission rates and initial product expansion. CAR T-cell persistence remains a significant issue, with the majority of relapses being antigen-positive after CAR T-cell infusion. Further, despite adding a second antigen, antigen-negative relapses have not yet been eliminated. This review summarizes the state of the art with dual-targeting CAR T cells for B-cell ALL and B-NHL, the challenges encountered, and possible next steps to overcome them.http://www.sciencedirect.com/science/article/pii/S2473952924007006 |
| spellingShingle | Gustavo de Oliveira Canedo Claire Roddie Persis J. Amrolia Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma Blood Advances |
| title | Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma |
| title_full | Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma |
| title_fullStr | Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma |
| title_full_unstemmed | Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma |
| title_short | Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma |
| title_sort | dual targeting car t cells for b cell acute lymphoblastic leukemia and b cell non hodgkin lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924007006 |
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