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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...

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Autores principales: Lorenz, Felix K.M., Ellinger, Christian, Kieback, Elisa, Wilde, Susanne, Lietz, Maria, Schendel, Dolores J., Uckert, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
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.
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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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