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Journal Article

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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Mansurkhodzhaev,  A.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Liepe,  J.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

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3181124.pdf
(Publisher version), 3MB

Supplementary Material (public)

3181124_Suppl.pdf
(Supplementary material), 317KB

Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0005-53A9-F
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.