Unbiased Identification of T-Cell Receptors Targeting Immunodominant Peptide-MHC Complexes for T-Cell Receptor Immunotherapy.
Hum Gene Ther
; 28(12): 1158-1168, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28950731
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*1501) and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*0702). 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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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Antígeno HLA-B7
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Transferência Adotiva
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Antígeno HLA-B15
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Neoplasias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article