Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jun;2(6):522-9.
doi: 10.1158/2326-6066.CIR-13-0227. Epub 2014 Mar 3.

HLA-binding properties of tumor neoepitopes in humans

Edward F Fritsch  1 , Mohini Rajasagi  2 , Patrick A Ott  2 , Vladimir Brusic  2 , Nir Hacohen  2 , Catherine J Wu  3
Affiliations
Review

HLA-binding properties of tumor neoepitopes in humans

Edward F Fritsch et al. Cancer Immunol Res. 2014 Jun.

Abstract

Cancer genome sequencing has enabled the rapid identification of the complete repertoire of coding sequence mutations within a patient's tumor and facilitated their use as personalized immunogens. Although a variety of techniques are available to assist in the selection of mutation-defined epitopes to be included within the tumor vaccine, the ability of the peptide to bind to patient MHC is a key gateway to peptide presentation. With advances in the accuracy of predictive algorithms for MHC class I binding, choosing epitopes on the basis of predicted affinity provides a rapid and unbiased approach to epitope prioritization. We show herein the retrospective application of a prediction algorithm to a large set of bona fide T cell-defined mutated human tumor antigens that induced immune responses, most of which were associated with tumor regression or long-term disease stability. The results support the application of this approach for epitope selection and reveal informative features of these naturally occurring epitopes to aid in epitope prioritization for use in tumor vaccines.

PubMed Disclaimer

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed

Figures

Figure 1
Figure 1
(A) The two faces of a bound peptide to the MHC and TCR molecules form a “double-sided key” that must be present in order to stimulate an antigen-specific immune response. Green--Anchor residues in the peptide that interact with MHC. Purple--Regions of the peptide that interact with the TCR surface. (B) A scatter plot of the predicted affinities of epitopes that stimulate detectable neoantigen T-cell responses, shown in Table 1. Group 1 epitopes demonstrate comparable predicted affinities of native and mutated peptides and were determined to have mutations in regions of the peptide critical for interactions with the TCR (dark purple – strong/moderate binders; light purple – weak binders). Group 2 epitopes (green) are mutated peptides with strong/moderate predicted affinity whose corresponding native peptides are not predicted to bind MHC, and were found to have mutations in the peptide residues critical for the interaction with MHC. Group 3 epitopes (grey) represent peptides where neither the native or mutated peptide are predicted to be HLA-binding peptides and may be either false negatives of the prediction algorithm or very low affinity functional epitopes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hacohen N, Fritsch EF, Carter TA, Lander ES, Wu C. Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol Res. 2013;1:11–15. - PMC - PubMed
    1. Heemskerk B, Kvistborg P, Schumacher TN. The cancer antigenome. EMBO J. 2013;32:194–203. - PMC - PubMed
    1. Castle JC, Kreiter S, Diekmann J, Lower M, van der Roemer N, de Graaf J, et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012;72:1081–1091. - PubMed
    1. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–218. - PMC - PubMed
    1. Berd D, Murphy G, Maguire HC, Jr, Mastrangelo MJ. Immunization with haptenized, autologous tumor cells induces inflammation of human melanoma metastases. Cancer Res. 1991;51:2731–2734. - PubMed

Publication types

MeSH terms