title: T-Cell Epitope Discovery for Therapeutic Cancer Vaccines.
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.
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA.|School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Sri
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA. Karen.Anderson.1@asu.edu.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
mesh_terms: D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
keywords: Cytotoxic CD8+ T cells; HLA typing; T-cell epitope