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 language | English (US) |
|---|---|
| Title of host publication | Methods in Molecular Biology |
| Publisher | Humana Press Inc. |
| Pages | 779-796 |
| Number of pages | 18 |
| Volume | 1403 |
| DOIs | |
| State | Published - Apr 1 2016 |
Publication series
| Name | Methods in Molecular Biology |
|---|---|
| Volume | 1403 |
| 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
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 proceeding › Chapter
}
TY - CHAP
T1 - T-cell epitope discovery for therapeutic cancer vaccines
AU - Krishna, Sri
AU - Anderson, Karen
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
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.
KW - Cytotoxic CD8 T cells
KW - HLA typing
KW - T-cell epitope
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U2 - 10.1007/978-1-4939-3387-7_45
DO - 10.1007/978-1-4939-3387-7_45
M3 - Chapter
VL - 1403
T3 - Methods in Molecular Biology
SP - 779
EP - 796
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -