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      The journey of CAR-T therapy in hematological malignancies

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          Abstract

          Chimeric antigen receptor T (CAR-T) cells therapy has revolutionized the treatment paradigms for hematological malignancies, with multi-line therapy-refractory patients achieving durable complete remissions (CR) and relatively high objective response rate (ORR). So far, many CAR-T products, such as Kymriah, Yescarta and Tecartus, have been developed and got the unprecedented results. However, some patients may relapse afterwards, driving intense investigations into promoting the development of novel strategies to overcome resistance and mechanisms of relapse. Notable technical progress, such as nanobodies and CRISPR-Case9, has also taken place to ensure CAR-T cell therapy fully satisfies its medical potential. In this review, we outline the basic principles for the development and manufacturing processes of CAR-T cell therapy, summarize the similarities and differences in efficacy of different products as well as their corresponding clinical results, and discuss CAR-T immunotherapy combined with other clinical effects of drug therapy.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12943-022-01663-0.

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          Most cited references119

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          Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

          In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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            Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

            In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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              Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

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                Author and article information

                Contributors
                dr.guanjiang@xzhmu.edu.cn
                Journal
                Mol Cancer
                Mol Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                8 October 2022
                8 October 2022
                2022
                : 21
                : 194
                Affiliations
                [1 ]GRID grid.413389.4, ISNI 0000 0004 1758 1622, Department of Dermatology, , Affiliated Hospital of Xuzhou Medical University, ; Xuzhou, Jiangsu China
                [2 ]GRID grid.417303.2, ISNI 0000 0000 9927 0537, Xuzhou Medical University, ; Xuzhou, Jiangsu China
                Article
                1663
                10.1186/s12943-022-01663-0
                9547409
                19c86983-c74a-4872-918a-441d92cf43da
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 July 2022
                : 21 September 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Oncology & Radiotherapy
                car-t cell therapy,hematological malignancies,targeted therapy,combinatorial therapy,drug product

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