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PDBsum entry 6o4z
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Immune system
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PDB id
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6o4z
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References listed in PDB file
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Key reference
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Title
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An in silico-In vitro pipeline identifying an hla-A02:01+ kras g12v+ spliced epitope candidate for a broad tumor-Immune response in cancer patients.
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Authors
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M.Mishto,
A.Mansurkhodzhaev,
G.Ying,
A.Bitra,
R.A.Cordfunke,
S.Henze,
D.Paul,
J.Sidney,
H.Urlaub,
J.Neefjes,
A.Sette,
D.M.Zajonc,
J.Liepe.
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Ref.
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Front Immunol, 2019,
10,
2572.
[DOI no: ]
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PubMed id
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Abstract
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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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