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      CAR-T cell potency: from structural elements to vector backbone components

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          Abstract

          Chimeric antigen receptor (CAR) T cell therapy, in which a patient’s own T lymphocytes are engineered to recognize and kill cancer cells, has achieved remarkable success in some hematological malignancies in preclinical and clinical trials, resulting in six FDA-approved CAR-T products currently available in the market. Once equipped with a CAR construct, T cells act as living drugs and recognize and eliminate the target tumor cells in an MHC-independent manner. In this review, we first described all structural modular of CAR in detail, focusing on more recent findings. We then pointed out behind-the-scene elements contributing to CAR expression and reviewed how CAR expression can be drastically affected by the elements embedded in the viral vector backbone.

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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
                marzieh.mazinani@yahoo.com
                rahbarif@modares.ac.ir
                Journal
                Biomark Res
                Biomark Res
                Biomarker Research
                BioMed Central (London )
                2050-7771
                19 September 2022
                19 September 2022
                2022
                : 10
                : 70
                Affiliations
                [1 ]GRID grid.412266.5, ISNI 0000 0001 1781 3962, Department of Medical Biotechnology, Faculty of Medical Sciences, , Tarbiat Modares University, ; P.O. Box 14115-111, Tehran, Iran
                [2 ]GRID grid.412266.5, ISNI 0000 0001 1781 3962, Research and Development Center of Biotechnology, , Tarbiat Modares University, ; Tehran, Iran
                Article
                417
                10.1186/s40364-022-00417-w
                9487061
                36123710
                bbeab7a0-004d-43ea-a97e-f45a036b5be8
                © 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
                : 15 May 2022
                : 7 September 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                chimeric antigen receptor,cancer immunotherapy,single-chain variable fragment,nanobody,lentiviral vectors,signal peptide

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