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The expansion of targetable biomarkers for CAR T cell therapy

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      Abstract

      Biomarkers are an integral part of cancer management due to their use in risk assessment, screening, differential diagnosis, prognosis, prediction of response to treatment, and monitoring progress of disease. Recently, with the advent of Chimeric Antigen Receptor (CAR) T cell therapy, a new category of targetable biomarkers has emerged. These biomarkers are associated with the surface of malignant cells and serve as targets for directing cytotoxic T cells. The first biomarker target used for CAR T cell therapy was CD19, a B cell marker expressed highly on malignant B cells. With the success of CD19, the last decade has shown an explosion of new targetable biomarkers on a range of human malignancies. These surface targets have made it possible to provide directed, specific therapy that reduces healthy tissue destruction and preserves the patient’s immune system during treatment. As of May 2018, there are over 100 clinical trials underway that target over 25 different surface biomarkers in almost every human tissue. This expansion has led to not only promising results in terms of patient outcome, but has also led to an exponential growth in the investigation of new biomarkers that could potentially be utilized in CAR T cell therapy for treating patients. In this review, we discuss the biomarkers currently under investigation and point out several promising biomarkers in the preclinical stage of development that may be useful as targets.

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          Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.

          T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies.
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            Author and article information

            Affiliations
            [1 ]ISNI 0000 0004 1936 9115, GRID grid.253294.b, Department of Microbiology and Molecular Biology, , Brigham Young University, ; 3142 LSB, Provo, UT 84602 USA
            [2 ]Thunder Biotech, Highland, UT USA
            Contributors
            mpassey8@gmail.com
            gajushrestha@gmail.com
            Richard_robison@byu.edu
            ORCID: http://orcid.org/0000-0002-8747-6217, 801-422-2449 , kim_oneill@byu.edu
            Journal
            J Exp Clin Cancer Res
            J. Exp. Clin. Cancer Res
            Journal of Experimental & Clinical Cancer Research : CR
            BioMed Central (London )
            0392-9078
            1756-9966
            21 July 2018
            21 July 2018
            2018
            : 37
            30031396
            6054736
            817
            10.1186/s13046-018-0817-0
            © The Author(s). 2018

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 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.

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            © The Author(s) 2018

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