Lost in the crowd: identifying targetable MHC class I neoepitopes for cancer immunotherapy

Eric A. Wilson, Karen Anderson

    Research output: Contribution to journalReview article

    1 Citation (Scopus)

    Abstract

    Introduction: The recent development of checkpoint blockade immunotherapy for cancer has led to impressive clinical results across multiple tumor types. There is mounting evidence that immune recognition of tumor derived MHC class I (MHC-I) restricted epitopes bearing cancer specific mutations and alterations is a crucial mechanism in successfully triggering immune-mediated tumor rejection. Therapeutic targeting of these cancer specific epitopes (neoepitopes) is emerging as a promising opportunity for the generation of personalized cancer vaccines and adoptive T cell therapies. However, one major obstacle limiting the broader application of neoepitope based therapies is the difficulty of selecting highly immunogenic neoepitopes among the wide array of presented non-immunogenic HLA ligands derived from self-proteins. Areas covered: In this review, we present an overview of the MHC-I processing and presentation pathway, as well as highlight key areas that contribute to the complexity of the associated MHC-I peptidome. We cover recent technological advances that simplify and optimize the identification of targetable neoepitopes for cancer immunotherapeutic applications. Expert commentary: Recent advances in computational modeling, bioinformatics, and mass spectrometry are unlocking the underlying mechanisms governing antigen processing and presentation of tumor-derived neoepitopes.

    Original languageEnglish (US)
    Pages (from-to)1065-1077
    Number of pages13
    JournalExpert Review of Proteomics
    Volume15
    Issue number12
    DOIs
    StatePublished - Dec 2 2018

    Fingerprint

    Immunotherapy
    Tumors
    Epitopes
    Neoplasms
    Bearings (structural)
    Cancer Vaccines
    T-cells
    Antigen Presentation
    Bioinformatics
    Processing
    Mountings
    Mass spectrometry
    Ligands
    Antigens
    Cell- and Tissue-Based Therapy
    Computational Biology
    Mass Spectrometry
    Proteins
    T-Lymphocytes
    Mutation

    Keywords

    • antigen processing
    • immunotherapy
    • mass spectrometry
    • MHC
    • neoepitopes
    • peptidome
    • prediction algorithms
    • T cell

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology

    Cite this

    Lost in the crowd : identifying targetable MHC class I neoepitopes for cancer immunotherapy. / Wilson, Eric A.; Anderson, Karen.

    In: Expert Review of Proteomics, Vol. 15, No. 12, 02.12.2018, p. 1065-1077.

    Research output: Contribution to journalReview article

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