Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Robinson, Ross A., McMurran, Catriona, McCully, Michelle L., Cole, David K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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
_version_ 1784600445159735296
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
work_keys_str_mv AT robinsonrossa engineeringsolubletcellreceptorsfortherapy
AT mcmurrancatriona engineeringsolubletcellreceptorsfortherapy
AT mccullymichellel engineeringsolubletcellreceptorsfortherapy
AT coledavidk engineeringsolubletcellreceptorsfortherapy