Gavriil, A;
Barisa, M;
Halliwell, E;
Anderson, J;
(2020)
Engineering Solutions for Mitigation of Chimeric Antigen Receptor T-Cell Dysfunction.
Cancers
, 12
(8)
, Article 2326. 10.3390/cancers12082326.
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Abstract
The clinical successes of chimeric antigen receptor (CAR)-T-cell therapy targeting cell surface antigens in B cell leukaemias and lymphomas has demonstrated the proof of concept that appropriately engineered T-cells have the capacity to destroy advanced cancer with long term remissions ensuing. Nevertheless, it has been significantly more problematic to effect long term clinical benefit in a solid tumour context. A major contributing factor to the clinical failure of CAR-T-cells in solid tumours has been named, almost interchangeably, as T-cell "dysfunction" or "exhaustion". While unhelpful ambiguity surrounds the term "dysfunction", "exhaustion" is canonically regarded as a pejorative term for T-cells. Recent understanding of T-cell developmental biology now identifies exhausted cells as vital for effective immune responses in the context of ongoing antigenic challenge. The purpose of this review is to explore the critical stages in the CAR-T-cell life-cycle and their various contributions to T-cell exhaustion. Through an appreciation of the predominant mechanisms of CAR-T-cell exhaustion and resultant dysfunction, we describe a range of engineering approaches to improve CAR-T-cell function.
| Type: | Article |
|---|---|
| Title: | Engineering Solutions for Mitigation of Chimeric Antigen Receptor T-Cell Dysfunction |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cancers12082326 |
| Publisher version: | https://doi.org/10.3390/cancers12082326 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | T cell dysfunction, T cell exhaustion, cancer immunotherapy, chimeric antigen receptor |
| UCL classification: | UCL 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 Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10109024 |
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