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.

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

SUBMITTER: Mishto M 

PROVIDER: S-EPMC6872521 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature