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      Clinical development of CAR T cell therapy in China: 2020 update

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          Abstract

          Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to the data from the clinicaltrials.gov website, China became the country with the most registered CAR T trials in September 2017. As of June 30, 2020, the number of registered CAR T trials in China has reached 357. In addition, as many as 150 other CAR T trials have been registered on ChiCTR. Although CAR T therapy is flourishing in China, there are still some problems that cannot be ignored. In this review, we aim to systematically summarize the clinical practice of CAR T-cell therapy in China. This review will provide an informative reference for colleagues in the field, and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.

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          Most cited references122

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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 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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              Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia

              BACKGROUND CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19–28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS A total of 53 adults received 19–28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19–28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, [Related object:] NCT01044069.)
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                Author and article information

                Contributors
                boj301@sina.com
                zhujun@csco.org.cn
                hanwdrsw69@yahoo.com
                Journal
                Cell Mol Immunol
                Cell Mol Immunol
                Cellular and Molecular Immunology
                Nature Publishing Group UK (London )
                1672-7681
                2042-0226
                30 September 2020
                30 September 2020
                April 2021
                : 18
                : 4
                : 792-804
                Affiliations
                [1 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Bio-Therapeutic, The First Medical Center, , Chinese PLA General Hospital, ; Beijing, 100853 China
                [2 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Hematology, The First Medical Center, , Chinese PLA General Hospital, ; Beijing, 100853 China
                [3 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Hematopoietic Stem Cell Transplantation, , The Fifth Medical Center, Chinese PLA General Hospital, ; Beijing, 100071 China
                [4 ]GRID grid.412474.0, ISNI 0000 0001 0027 0586, Key Laboratory of Carcinogenesis and Translational Research, Departments of Lymphoma, Radiology and Nuclear Medicine, , Peking University Cancer Hospital and Institute, ; Beijing, 100036 China
                Author information
                http://orcid.org/0000-0003-3207-3899
                Article
                555
                10.1038/s41423-020-00555-x
                8115146
                32999455
                a43e0309-25bb-4a24-ba65-a4639cce4914
                © CSI and USTC 2020

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 August 2020
                : 4 September 2020
                : 8 September 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81830002
                Award ID: 31991171
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s), under exclusive licence to CSI and USTC 2021

                Immunology
                chimeric antigen receptor,clinical trials,china,cancer immunotherapy,targeted therapies
                Immunology
                chimeric antigen receptor, clinical trials, china, cancer immunotherapy, targeted therapies

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