T-cell epitope discovery for therapeutic cancer vaccines

Sri Krishna, Karen Anderson

    Research output: Chapter in Book/Report/Conference proceedingChapter

    5 Citations (Scopus)

    Abstract

    The success of recent immune checkpoint blockade trials in solid tumors has demonstrated the tremendous potential of immune-mediated treatment strategies for cancer therapy. These immune therapies activate preexisting cytotoxic CD8+ T cells (CTL) to selectively target and eradicate malignant cells. In vitro models suggest that these therapies may be more effective in combination with priming of CTL using cancer vaccines. CTL-mediated tumor targeting is achieved by its recognition of tumor antigenic epitopes presented on human leukocyte antigen (HLA) class I molecules by tumor cells. Discovering CTL-antigenic epitopes is therefore central to the design of therapeutic T-cell vaccines and immune monitoring of these complex immunotherapies. However, selecting and monitoring T-cell epitopes remains difficult due to the extensive polymorphism of HLA alleles and the presence of confounding non-immunogenic self-peptides. To overcome these challenges, this chapter presents methodologies for the design of CTL-targeted vaccines using selection of target HLA alleles, novel integrated computational strategies to predict HLA-class I CTL epitopes, and epitope validation methods using short-term ex vivo T-cell stimulation. This strategy results in the improved efficiency for selecting antigenic epitopes for CTL-mediated vaccines and for immune monitoring of tumor antigens.

    Original languageEnglish (US)
    Title of host publicationMethods in Molecular Biology
    PublisherHumana Press Inc.
    Pages779-796
    Number of pages18
    Volume1403
    DOIs
    StatePublished - Apr 1 2016

    Publication series

    NameMethods in Molecular Biology
    Volume1403
    ISSN (Print)10643745

    Fingerprint

    Cancer Vaccines
    T-Lymphocyte Epitopes
    HLA Antigens
    T-Lymphocytes
    Immunologic Monitoring
    Vaccines
    Neoplasms
    Epitopes
    Therapeutics
    Alleles
    Neoplasm Antigens
    Antigen-Antibody Complex
    Immunotherapy
    Peptides

    Keywords

    • Cytotoxic CD8 T cells
    • HLA typing
    • T-cell epitope

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics

    Cite this

    Krishna, S., & Anderson, K. (2016). T-cell epitope discovery for therapeutic cancer vaccines. In Methods in Molecular Biology (Vol. 1403, pp. 779-796). (Methods in Molecular Biology; Vol. 1403). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-3387-7_45

    T-cell epitope discovery for therapeutic cancer vaccines. / Krishna, Sri; Anderson, Karen.

    Methods in Molecular Biology. Vol. 1403 Humana Press Inc., 2016. p. 779-796 (Methods in Molecular Biology; Vol. 1403).

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Krishna, S & Anderson, K 2016, T-cell epitope discovery for therapeutic cancer vaccines. in Methods in Molecular Biology. vol. 1403, Methods in Molecular Biology, vol. 1403, Humana Press Inc., pp. 779-796. https://doi.org/10.1007/978-1-4939-3387-7_45
    Krishna S, Anderson K. T-cell epitope discovery for therapeutic cancer vaccines. In Methods in Molecular Biology. Vol. 1403. Humana Press Inc. 2016. p. 779-796. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-3387-7_45
    Krishna, Sri ; Anderson, Karen. / T-cell epitope discovery for therapeutic cancer vaccines. Methods in Molecular Biology. Vol. 1403 Humana Press Inc., 2016. pp. 779-796 (Methods in Molecular Biology).
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