PMID- 27076167 OWN - NLM STAT- MEDLINE DCOM- 20161221 LR - 20161230 IS - 1940-6029 (Electronic) IS - 1064-3745 (Linking) VI - 1403 DP - 2016 TI - T-Cell Epitope Discovery for Therapeutic Cancer Vaccines. PG - 779-96 LID - 10.1007/978-1-4939-3387-7_45 [doi] AB - 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. FAU - Krishna, Sri AU - Krishna S AD - Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA. AD - School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA. FAU - Anderson, Karen S AU - Anderson KS AD - Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA. Karen.Anderson.1@asu.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Methods Mol Biol JT - Methods in molecular biology (Clifton, N.J.) JID - 9214969 RN - 0 (Cancer Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) SB - IM MH - Alleles MH - CD8-Positive T-Lymphocytes/immunology MH - Cancer Vaccines/*immunology MH - Computational Biology/*methods MH - Epitopes, T-Lymphocyte/*immunology MH - HLA Antigens/genetics/immunology MH - Humans OTO - NOTNLM OT - Cytotoxic CD8+ T cells OT - HLA typing OT - T-cell epitope EDAT- 2016/04/15 06:00 MHDA- 2016/12/22 06:00 CRDT- 2016/04/15 06:00 PHST- 2016/04/15 06:00 [entrez] PHST- 2016/04/15 06:00 [pubmed] PHST- 2016/12/22 06:00 [medline] AID - 10.1007/978-1-4939-3387-7_45 [doi] PST - ppublish SO - Methods Mol Biol. 2016;1403:779-96. doi: 10.1007/978-1-4939-3387-7_45.