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
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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 LiepeAbstract
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.
Journal details
Journal Frontiers in Immunology
Volume 10
Pages 2572
Available online
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Full text links
Publisher website (DOI) 10.3389/fimmu.2019.02572
Europe PubMed Central 31803176
Pubmed 31803176
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