T-Cell Epitope Discovery for Therapeutic Cancer Vaccines

Methods Mol Biol. 2016:1403:779-96. doi: 10.1007/978-1-4939-3387-7_45.

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.

Keywords: Cytotoxic CD8+ T cells; HLA typing; T-cell epitope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Computational Biology / methods*
  • Epitopes, T-Lymphocyte / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans

Substances

  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA Antigens