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  An in silico-in vitro pipeline identifying an HLA-A*02:01+ KRAS G12V+ spliced epitope candidate for a broad tumor-immune response in cancer patients.

Mishto, M., Mansurkhodzhaev, A., Ying, G., Bitra, A., Cordfunke, R. A., Henze, S., et al. (2019). An in silico-in vitro pipeline identifying an HLA-A*02:01+ KRAS G12V+ spliced epitope candidate for a broad tumor-immune response in cancer patients. Frontiers in Immunology, 10: 2572. doi:10.3389/fimmu.2019.02572.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-53A9-F Version Permalink: http://hdl.handle.net/21.11116/0000-0005-620C-0
Genre: Journal Article

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 Creators:
Mishto, M., Author
Mansurkhodzhaev, A.1, Author              
Ying, G., Author
Bitra, A., Author
Cordfunke, R. A., Author
Henze, S., Author
Paul, D., Author
Sidney, J., Author
Urlaub, H.2, Author              
Neefjes, J., Author
Sette, A., Author
Zajonc, D. M., Author
Liepe, J.1, Author              
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: KRAS; adoptive T cell therapy targets; antigen presentation; cancer epitopes; peptide splicing; proteasome; tumor immunology
 Abstract: Targeting CD8+ T cells to recurrent tumor-specific mutations can profoundly contribute to cancer treatment. Some of these mutations are potential tumor antigens although they can be displayed by non-spliced epitopes only in a few patients, because of the low affinity of the mutated non-spliced peptides for the predominant HLA class I alleles. Here, we describe a pipeline that uses the large sequence variety of proteasome-generated spliced peptides and identifies spliced epitope candidates, which carry the mutations and bind the predominant HLA-I alleles with high affinity. They could be used in adoptive T cell therapy and other anti-cancer immunotherapies for large cohorts of cancer patients. As a proof of principle, the application of this pipeline led to the identification of a KRAS G12V mutation-carrying spliced epitope candidate, which is produced by proteasomes, transported by TAPs and efficiently presented by the most prevalent HLA class I molecules, HLA-A*02:01 complexes.

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Language(s): eng - English
 Dates: 2019-11-152019
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.3389/fimmu.2019.02572
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Title: Frontiers in Immunology
Source Genre: Journal
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Pages: 17 Volume / Issue: 10 Sequence Number: 2572 Start / End Page: - Identifier: -