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- W1995925437 abstract "NY-ESO-1 is a cancer/germline antigen (Ag) with distinctively strong immunogenicity. We have previously demonstrated that NY-ESO-1 serves as an endogenous adjuvant by engaging dendritic cell (DC)-surface receptors of calreticulin (CRT) and toll-like receptor (TLR) 4. In the present study, NY-ESO-1 was investigated for its immunomodulatory roles as a molecular adjuvant in whole-tumor cell vaccines using the Renca kidney cancer model. Renca cells were genetically engineered to express NY-ESO-1 on the cell surface to enhance direct interactions with DC. The effect of ectopic cell-surface expression of NY-ESO-1 was investigated on tumor immunogenicity, DC activation, cytotoxic T lymphocytes against model tumor-associated Ags, and the effectiveness of the modified tumor cells as a therapeutic whole-cell vaccine. Cell-surface expression of NY-ESO-1 was able to reduce the tumor growth of Renca cells in BALB/c mice, although the modification did not alter cell proliferation rate in vitro. Directly engaging the innate immune system through NY-ESO-1 facilitated the interaction of tumor cells with DC, leading to enhanced DC activation and subsequent tumor-specific T-cell priming. When used as a therapeutic whole-cell vaccine, Renca cells with NY-ESO-1 on the surface mediated stronger inhibitory effects on tumor growth and metastasis compared with parental Renca or Renca cells expressing a control protein GFP on the surface. Augmented antitumor efficacy correlated with increased CD8+ T-cell infiltration into tumors and decreased myeloid-derived suppressor cells and regulatory T cells in the spleen. As a cancer/germline Ag and as an immunomodulatory adjuvant through engaging innate immune receptors, NY-ESO-1 offers a unique opportunity for improved whole-tumor cell vaccinations upon the classic GM-CSF-engineered cell vaccines." @default.
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- W1995925437 date "2013-10-01" @default.
- W1995925437 modified "2023-10-02" @default.
- W1995925437 title "Enhancing Whole-Tumor Cell Vaccination by Engaging Innate Immune System Through NY-ESO-1/Dendritic Cell Interactions" @default.
- W1995925437 doi "https://doi.org/10.1097/cji.0b013e3182a80263" @default.
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