T-cell epitope discovery for therapeutic cancer vaccines

Sri Krishna, Karen Anderson

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

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

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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