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Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy
T-cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best-suited major histocompatibility complex (MHC) molecules of cance...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737719/ https://www.ncbi.nlm.nih.gov/pubmed/28950731 http://dx.doi.org/10.1089/hum.2017.122 |
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author | Lorenz, Felix K.M. Ellinger, Christian Kieback, Elisa Wilde, Susanne Lietz, Maria Schendel, Dolores J. Uckert, Wolfgang |
author_facet | Lorenz, Felix K.M. Ellinger, Christian Kieback, Elisa Wilde, Susanne Lietz, Maria Schendel, Dolores J. Uckert, Wolfgang |
author_sort | Lorenz, Felix K.M. |
collection | PubMed |
description | T-cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best-suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. We generated an MHC cell library and developed a platform approach to detect, isolate, and re-express TCRs specific for immunodominant pMHCs. The platform approach was applied to identify a human papillomavirus (HPV16) oncogene E5-specific TCR, recognizing a novel, naturally processed pMHC (HLA-B*15:01) and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*07:02). The platform provides a useful tool to isolate in an unbiased manner TCRs specific for novel and immunodominant pMHC targets for use in TCR immunotherapy. |
format | Online Article Text |
id | pubmed-5737719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Mary Ann Liebert, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57377192017-12-21 Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy Lorenz, Felix K.M. Ellinger, Christian Kieback, Elisa Wilde, Susanne Lietz, Maria Schendel, Dolores J. Uckert, Wolfgang Hum Gene Ther Research Articles T-cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best-suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. We generated an MHC cell library and developed a platform approach to detect, isolate, and re-express TCRs specific for immunodominant pMHCs. The platform approach was applied to identify a human papillomavirus (HPV16) oncogene E5-specific TCR, recognizing a novel, naturally processed pMHC (HLA-B*15:01) and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*07:02). The platform provides a useful tool to isolate in an unbiased manner TCRs specific for novel and immunodominant pMHC targets for use in TCR immunotherapy. Mary Ann Liebert, Inc. 2017-12-01 2017-12-01 /pmc/articles/PMC5737719/ /pubmed/28950731 http://dx.doi.org/10.1089/hum.2017.122 Text en © Felix K.M. Lorenz et al. 2017; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Lorenz, Felix K.M. Ellinger, Christian Kieback, Elisa Wilde, Susanne Lietz, Maria Schendel, Dolores J. Uckert, Wolfgang Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title | Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title_full | Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title_fullStr | Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title_full_unstemmed | Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title_short | Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide–MHC Complexes for T-Cell Receptor Immunotherapy |
title_sort | unbiased identification of t-cell receptors targeting immunodominant peptide–mhc complexes for t-cell receptor immunotherapy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737719/ https://www.ncbi.nlm.nih.gov/pubmed/28950731 http://dx.doi.org/10.1089/hum.2017.122 |
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