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      CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges

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          Abstract

          Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-related coagulopathy. In addition, due to antigen escape, the limited CAR-T cell persistence, and immunosuppressive tumor microenvironment, a considerable proportion of patients relapse after CAR-T cell therapy. Thus, in this review, we focus on the progress and challenges of CAR-T cell therapy in hematological malignancies, such as attractive therapeutic targets, CAR-T related toxicities, and resistance to CAR-T cell therapy, and provide some practical recommendations.

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          Most cited references268

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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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              Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

              Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                10 June 2022
                2022
                : 13
                : 927153
                Affiliations
                [1] 1 Department of Hematology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                [2] 2 Institute of Clinical Medicine College, Guangzhou University of Chinese Medicine , Guangzhou, China
                [3] 3 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University , Guangzhou, China
                [4] 4 School of Medicine, Jishou University , Jishou, China
                [5] 5 Department of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital , Shenzhen, China
                Author notes

                Edited by: Katy Rezvani, University of Texas MD Anderson Cancer Center, United States

                Reviewed by: Katherina Psarra, Evaggelismos General Hospital, Greece; Ali Roghanian, University of Southampton, United Kingdom

                *Correspondence: Yang Xiao, jdxiao111@ 123456163.com

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.927153
                9226391
                35757715
                1139d9eb-0876-42a5-a7e9-d5ca1fe2292a
                Copyright © 2022 Zhang, Zhu, Zhang, Chen and Xiao

                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.

                History
                : 23 April 2022
                : 16 May 2022
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 270, Pages: 20, Words: 9016
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Funded by: Basic and Applied Basic Research Foundation of Guangdong Province , doi 10.13039/501100021171;
                Categories
                Immunology
                Review

                Immunology
                car-t cell,hematological malignancies,car-t related toxicities,antigen escape,immunosuppressive tumor microenvironment,combinatorial therapy

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