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Engineering soluble T‐cell receptors for therapy
Immunotherapy approaches that target peptide–human leukocyte antigen (pHLA) complexes are becoming highly attractive because of their potential to access virtually all foreign and cellular proteins. For this reason, there has been considerable interest in the development of the natural ligand for pH...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596704/ https://www.ncbi.nlm.nih.gov/pubmed/33624424 http://dx.doi.org/10.1111/febs.15780 |
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author | Robinson, Ross A. McMurran, Catriona McCully, Michelle L. Cole, David K. |
author_facet | Robinson, Ross A. McMurran, Catriona McCully, Michelle L. Cole, David K. |
author_sort | Robinson, Ross A. |
collection | PubMed |
description | Immunotherapy approaches that target peptide–human leukocyte antigen (pHLA) complexes are becoming highly attractive because of their potential to access virtually all foreign and cellular proteins. For this reason, there has been considerable interest in the development of the natural ligand for pHLA, the T‐cell receptor (TCR), as a soluble drug to target disease‐associated pHLA presented at the cell surface. However, native TCR stability is suboptimal for soluble drug development, and natural TCRs generally have weak affinities for pHLAs, limiting their potential to reach efficacious receptor occupancy levels as soluble drugs. To overcome these limitations and make full use of the TCR as a soluble drug platform, several protein engineering solutions have been applied to TCRs to enhance both their stability and affinity, with a focus on retaining target specificity and selectivity. Here, we review these advances and look to the future for the next generation of soluble TCR‐based therapies that can target monomorphic HLA‐like proteins presenting both peptide and nonpeptide antigens. |
format | Online Article Text |
id | pubmed-8596704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85967042021-11-22 Engineering soluble T‐cell receptors for therapy Robinson, Ross A. McMurran, Catriona McCully, Michelle L. Cole, David K. FEBS J State‐of‐the‐Art Reviews Immunotherapy approaches that target peptide–human leukocyte antigen (pHLA) complexes are becoming highly attractive because of their potential to access virtually all foreign and cellular proteins. For this reason, there has been considerable interest in the development of the natural ligand for pHLA, the T‐cell receptor (TCR), as a soluble drug to target disease‐associated pHLA presented at the cell surface. However, native TCR stability is suboptimal for soluble drug development, and natural TCRs generally have weak affinities for pHLAs, limiting their potential to reach efficacious receptor occupancy levels as soluble drugs. To overcome these limitations and make full use of the TCR as a soluble drug platform, several protein engineering solutions have been applied to TCRs to enhance both their stability and affinity, with a focus on retaining target specificity and selectivity. Here, we review these advances and look to the future for the next generation of soluble TCR‐based therapies that can target monomorphic HLA‐like proteins presenting both peptide and nonpeptide antigens. John Wiley and Sons Inc. 2021-03-10 2021-11 /pmc/articles/PMC8596704/ /pubmed/33624424 http://dx.doi.org/10.1111/febs.15780 Text en © 2021 Immunocare. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | State‐of‐the‐Art Reviews Robinson, Ross A. McMurran, Catriona McCully, Michelle L. Cole, David K. Engineering soluble T‐cell receptors for therapy |
title | Engineering soluble T‐cell receptors for therapy |
title_full | Engineering soluble T‐cell receptors for therapy |
title_fullStr | Engineering soluble T‐cell receptors for therapy |
title_full_unstemmed | Engineering soluble T‐cell receptors for therapy |
title_short | Engineering soluble T‐cell receptors for therapy |
title_sort | engineering soluble t‐cell receptors for therapy |
topic | State‐of‐the‐Art Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596704/ https://www.ncbi.nlm.nih.gov/pubmed/33624424 http://dx.doi.org/10.1111/febs.15780 |
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