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The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells
The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to bo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981602/ https://www.ncbi.nlm.nih.gov/pubmed/31892219 http://dx.doi.org/10.3390/ijms21010204 |
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author | Hughes-Parry, Hannah E. Cross, Ryan S. Jenkins, Misty R. |
author_facet | Hughes-Parry, Hannah E. Cross, Ryan S. Jenkins, Misty R. |
author_sort | Hughes-Parry, Hannah E. |
collection | PubMed |
description | The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to both the ecto- and endo-domains of the CAR, with recent designs targeting multiple antigens and including inducible elements. These developments are likely to play an important role in inducing effective CAR T cell responses in a solid tumour context, where clinical responses have not been effective to date. This review highlights the spectrum of novel strategies being employed in CAR design, including for example variations in targeting tumour antigens by utilising different ectodomain designs such as dual chain CARs, natural receptor or ligand-based CARs, and T cell receptor fusion constructs, and also reviews some of the innovative approaches to a “universal” CAR and various multi-antigen targeting CAR strategies. We also explore how choices in the endodomain impact CAR function and how these need to be considered in the overall CAR design. |
format | Online Article Text |
id | pubmed-6981602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69816022020-02-03 The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells Hughes-Parry, Hannah E. Cross, Ryan S. Jenkins, Misty R. Int J Mol Sci Review The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to both the ecto- and endo-domains of the CAR, with recent designs targeting multiple antigens and including inducible elements. These developments are likely to play an important role in inducing effective CAR T cell responses in a solid tumour context, where clinical responses have not been effective to date. This review highlights the spectrum of novel strategies being employed in CAR design, including for example variations in targeting tumour antigens by utilising different ectodomain designs such as dual chain CARs, natural receptor or ligand-based CARs, and T cell receptor fusion constructs, and also reviews some of the innovative approaches to a “universal” CAR and various multi-antigen targeting CAR strategies. We also explore how choices in the endodomain impact CAR function and how these need to be considered in the overall CAR design. MDPI 2019-12-27 /pmc/articles/PMC6981602/ /pubmed/31892219 http://dx.doi.org/10.3390/ijms21010204 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hughes-Parry, Hannah E. Cross, Ryan S. Jenkins, Misty R. The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title | The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title_full | The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title_fullStr | The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title_full_unstemmed | The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title_short | The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells |
title_sort | evolving protein engineering in the design of chimeric antigen receptor t cells |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981602/ https://www.ncbi.nlm.nih.gov/pubmed/31892219 http://dx.doi.org/10.3390/ijms21010204 |
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