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Unbiased identification of T cell receptors targeting immunodominant peptide-MHC complexes for T cell receptor immunotherapy

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Item Type:Article
Title:Unbiased identification of T cell receptors targeting immunodominant peptide-MHC complexes for T cell receptor immunotherapy
Creators Name:Lorenz, F.K.M. and Ellinger, C. and Kieback, E. and Wilde, S. and Lietz, M. and Schendel, D.J. and Uckert, W.
Abstract: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.
Keywords:Immunotherapy, T Cell Receptor (TCR) Discovery, TCR Gene Therapy, MHC Cell Library, Immunodominance, Human Papillomavirus ES
Source:Human Gene Therapy
ISSN:1043-0342
Publisher:Mary Ann Liebert (U.S.A.)
Volume:28
Number:12
Page Range:1158-1168
Date:1 December 2017
Additional Information:Copyright © Felix K.M. Lorenz et al.
Official Publication:https://doi.org/10.1089/hum.2017.122
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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