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High sensitivity of cancer exome-based CD8 T cell neo-antigen identification

Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of...

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Detalles Bibliográficos
Autores principales: van Buuren, Marit M, Calis, Jorg JA, Schumacher, Ton NM
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106163/
https://www.ncbi.nlm.nih.gov/pubmed/25083320
http://dx.doi.org/10.4161/onci.28836
Descripción
Sumario:Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of these findings. Work from several groups has demonstrated that novel tumor-specific antigens can be discovered through the use of cancer exome sequencing data, thereby providing a potential pipeline for the development of patient-specific vaccines. Importantly though, it has not been established which fraction of cancer neo-antigens that can be recognized by CD8(+) T cells is successfully uncovered with the current exome-based epitope prediction strategies. Here, we use a data set comprising human cancer neo-antigens that was previously identified through the use of unbiased, computational-independent strategies to describe the potential of cancer exome-based neo-antigen discovery. This analysis shows a high sensitivity of exome-guided neo-antigen prediction of approximately 70%. We propose that future research should focus on the analysis and optimization of the specificity of neo-antigen prediction, and should undoubtedly entail the clinical evaluation of patient-specific vaccines with the aim of inducing immunoreactivity against tumor-displayed neo-antigens in a physiologically relevant context.