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T-cell receptor gene-modified cells: past promises, present methodologies and future challenges

Rego, RT; Morris, EC; Lowdell, MW; (2019) T-cell receptor gene-modified cells: past promises, present methodologies and future challenges. Cytotherapy , 21 (3) pp. 341-357. 10.1016/j.jcyt.2018.12.002.

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Abstract

Immunotherapy constitutes an exciting and rapidly evolving field, and the demonstration that genetically modified T-cell receptors (TCRs) can be used to produce T-lymphocyte populations of desired specificity offers new opportunities for antigen-specific T-cell therapy. Overall, TCR-modified T cells have the ability to target a wide variety of self and non–self targets through the normal biology of a T cell. Although major histocompatibility complex (MHC)–restricted and dependent on co-receptors, genetically engineered TCRs still present a number of characteristics that ensure they are an important alternative strategy to chimeric antigen receptors (CARs), and high-affinity TCRs can now be successfully engineered with the potential to enhance therapeutic efficacy while minimizing adverse events. This review will focus on the main characteristics of TCR gene-modified cells, their potential clinical application and promise to the field of adoptive cell transfer (ACT), basic manufacturing procedures and characterization protocols and overall challenges that need to be overcome so that redirection of TCR specificity may be successfully translated into clinical practice, beyond early-phase clinical trials.

Type: Article
Title: T-cell receptor gene-modified cells: past promises, present methodologies and future challenges
DOI: 10.1016/j.jcyt.2018.12.002
Publisher version: https://doi.org/10.1016/j.jcyt.2018.12.002
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Biotechnology & Applied Microbiology, Cell Biology, Hematology, Medicine, Research & Experimental, Research & Experimental Medicine, adoptive cell therapy, gene therapy, immunotherapy, T-cell receptor-modified cells, CHIMERIC ANTIGEN RECEPTOR, HEPATITIS-B-VIRUS, MHC CLASS-I, IMMUNE CHECKPOINT BLOCKADE, ADOPTIVE IMMUNOTHERAPY, CANCER REGRESSION, ANTI-PD-1 ANTIBODY, HUMAN-LYMPHOCYTES, TUMOR-CELLS, TCR
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10080490
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