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- W3000505586 abstract "ABSTRACT We demonstrate the first preclinical proof-of-concept of a mutation-based individualized cancer vaccine. Multiple genetic events and subsequent clonal evolution drive carcinogenesis, making disease elimination with single targeted drugs difficult. The multiplicity of gene mutations derived from clonal heterogeneity therefore represents an ideal setting for multi-epitope tumor vaccination. Here we used NGS exome resequencing to identify 941 non-synonymous somatic point mutations in B16F10 murine melanoma cells, with 589 of those mutations in expressed genes. Potential driver mutations occurred in classical tumor suppressor genes and genes involved in proto-oncogenic signaling pathways that control cell proliferation, adhesion, migration and apoptosis. The immunogenicity and specificity of 50 validated mutations was determined by immunizing mice with long peptides encoding the mutated epitopes. One-third of these peptides were found to be immunogenic, with 60 % in this group eliciting immune responses directed preferentially against the mutated sequence as compared to the wild type sequence. In tumor transplant models, peptide immunization conferred in vivo tumor control in protective and therapeutic settings, thereby qualifying mutated epitopes that include single amino acid substitutions as effective vaccines. Not only do our findings provide the first comprehensive picture of the mutanome of B16F10 melanoma, the most widely used cell line in immunotherapy studies, they also they offer insight into the extent of the immunogenicity of non-synonymous base substitution mutations. Lastly, the findings demonstrate the use of deep sequencing to identify immunogenic mutations and paves the way for individualized immunotherapy of cancer patients." @default.
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- W3000505586 date "2012-06-01" @default.
- W3000505586 modified "2023-10-15" @default.
- W3000505586 title "P2.06 Exploiting The Mutanome for Tumor Vaccination" @default.
- W3000505586 doi "https://doi.org/10.1016/s0923-7534(20)31329-6" @default.
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