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• W1531963926 abstract "The cancer/testis antigen NY-ESO-1 contains an immunodominant HLA-A2-binding peptide (SLLMWITQC), designated S9C, an attractive target for vaccination against several human cancers. As cysteine contains a reactive SH, the oxidation status of exogenous synthetic peptide is uncertain. We have designed tolerance-breaking DNA fusion vaccines incorporating a domain of tetanus toxin fused to tumor-derived peptide sequences (p.DOM-peptide), placed at the C-terminus for optimal immunogenicity. In a “humanized” HLA-A2 preclinical model, p.DOM-S9C primed S9C-specific CD8+ T cells more effectively than adjuvanted synthetic peptide. A DNA vaccine encoding the full NY-ESO-1 sequence alone induced only weak S9C-specific responses, amplified by addition of DOM sequence. The analog peptide (SLLMWITQL) also primed peptide-specific CD8+ T cells, again increased by DNA delivery. Importantly, T cells induced by S9C-encoding DNA vaccines killed tumor cells expressing endogenous NY-ESO-1. Only a fraction of T cells induced by the S9L-encoding DNA vaccines was able to recognize S9C and kill tumor cells. These data indicate that DNA vaccines mimic posttranslational modifications of SH-containing peptides expressed by tumor cells. Instability of synthetic peptides and the potential dangers of analog peptides contrast with the ability of DNA vaccines to induce high levels of tumor-lytic peptide-specific CD8+ T cells. These findings encourage clinical exploration of this vaccine strategy to target NY-ESO-1." @default.
• W1531963926 created "2016-06-24" @default.
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• W1531963926 date "2013-04-11" @default.
• W1531963926 modified "2023-09-23" @default.
• W1531963926 title "DNA fusion vaccine designs to induce tumor-lytic CD8+ T-cell attack via the immunodominant cysteine-containing epitope of NY-ESO 1" @default.
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• W1531963926 doi "https://doi.org/10.1002/ijc.28156" @default.
• W1531963926 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23494538" @default.
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