PuSH - Publication Server of Helmholtz Zentrum München: Unbiased identification of T-cell receptors Targeting immunodominant peptide-MHC complexes for T-cell receptor immunotherapy.

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Lorenz, F.K.* ; Ellinger, C. ; Kieback, E.* ; Wilde, S. ; Lietz, M.* ; Schendel, D.J. ; Uckert, W.*

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

Hum. Gene Ther. 28, 1158-1168 (2017)

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Open Access Green as soon as Postprint is submitted to ZB.

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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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