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Hum Gene Ther ; 28(12): 1158-1168, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28950731

RESUMO

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.


Assuntos
Transferência Adotiva/métodos , Antígeno HLA-B15 , Antígeno HLA-B7 , Neoplasias , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T , Linfócitos T/imunologia , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Antígeno HLA-B7/genética , Antígeno HLA-B7/imunologia , Humanos , Células K562 , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Peptídeos/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
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