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The identification of novel biomarkers and therapeutic targets in advanced cancer is critical for improving cancer diagnosis and therapeutics. Survivin (SV) is highly expressed predominantly in most cancer cells and tissues but is absent or undetectable in terminally differentiated normal adult tissues. Therefore, it functions as an almost universal tumor antigen. Peptides are short chains of amino acids linked by peptide bonds. To obtain novel SV decamers that are able to induce SV-specific cytotoxic T lymphocytes (CTLs) with a higher cytotoxic efficiency against cancer cells, major histocompatibility complex (MHC) peptide binding algorithms were conducted to predict nine modified SV 95  decamers (from SV 95–2  to SV 95–10 ) based on the natural SV 95–104  peptide sequence of ELTLGEFLKL (here defined as SV 95–1 ). The fluorescent density of each SV 95  peptide was determined by a MHC stability assay, followed by the generation of SV 95 -specific CTLs with each SV 95  peptide (from SV 95–1  to SV 95–10 ) and human dendritic cells (DCs) loaded with Poly(lactic- co -glycolic) acid (PLGA) nanoparticles encapsulated with SV 95  peptide. Finally, IFN-γ ELISpot and CytoTox 96 ®  Non-Radioactive Cytotoxicity Assays were employed to verify their cytotoxic efficiency of the SV 95 -specific CTLs generated with the corresponding artificial antigen presenting cells (aAPCs) containing SV 95  (SV 95–1  to SV 95–10 ) peptide. Furthermore, the cytotoxicity of the SV 95  specific CTLs generated with nine mutated SV 95  peptides was compared to the one generated with natural SV 95–1  peptide and TIL2080  cells . The results indicated that the HLA-A2-restricted mutated SV 95  epitope decamers (SV 95–6  and SV 95–7 ) showed significant higher binding ability compared to natural peptide SV 95–1  in MHC stability assay. More importantly, SV 95– specific CTLs with higher cytotoxicity were successfully induced with both SV 95–6  and SV 95–7  peptides, which significantly eliminated target cells (not only SV 95–1  peptide pulsed T2 cells, but also both HLA-A2 and SV positive cancer cells) when compared to those generated with natural SV 95–1  peptide and TIL2080 cells. These findings suggest that the SV 95–6  and SV 95–7  peptides are two novel HLA-A2-restricted CTL epitopes and may be useful for the immunotherapy for patients with survivin expressing cancer.

Novel Survivin Peptides Screened With Computer Algorithm Induce Cytotoxic T Lymphocytes With Higher Cytotoxic Efficiency to Cancer Cells