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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

Authors :
Michele Mishto
Artem Mansurkhodzhaev
Ge Ying
Aruna Bitra
Robert A. Cordfunke
Sarah Henze
Debdas Paul
John Sidney
Henning Urlaub
Jacques Neefjes
Alessandro Sette
Dirk M. Zajonc
Juliane Liepe
Source :
Frontiers in Immunology, Frontiers in Immunology, 10, Mishto, M, Mansurkhodzhaev, A, Ying, G, Bitra, A, Cordfunke, R A, Henze, S, Paul, D, Sidney, J, Urlaub, H, Neefjes, J, Sette, A, Zajonc, D M & Liepe, J 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, vol. 10, 2572 . https://doi.org/10.3389/fimmu.2019.02572, Frontiers in Immunology, 10. FRONTIERS MEDIA SA, Frontiers in Immunology, Vol 10 (2019)
Publication Year :
2019

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. peerReviewed

Details

Language :
English
Database :
OpenAIRE
Journal :
Frontiers in Immunology, Frontiers in Immunology, 10, Mishto, M, Mansurkhodzhaev, A, Ying, G, Bitra, A, Cordfunke, R A, Henze, S, Paul, D, Sidney, J, Urlaub, H, Neefjes, J, Sette, A, Zajonc, D M & Liepe, J 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, vol. 10, 2572 . https://doi.org/10.3389/fimmu.2019.02572, Frontiers in Immunology, 10. FRONTIERS MEDIA SA, Frontiers in Immunology, Vol 10 (2019)
Accession number :
edsair.doi.dedup.....d399f099abb20701897a67c70041664f
Full Text :
https://doi.org/10.3389/fimmu.2019.02572