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• W3157585303 abstract "Background: Harnessing the immune system to purposely recognize and destroy tumours represents a significant breakthrough in clinical oncology. Nonsynonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies including cancer vaccines as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multi-target vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform. Methods: Here we identified mutations of murine mammary carcinoma cells by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click-chemistry method for easy preparation of vaccines against mouse mammary carcinoma. Results: As compared to short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells which readily produced IFN-γ and TNF-α. The resulting anti-tumour effect was associated with favourable immune re-polarization in the tumour microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumour recurrence and metastases, and prolonged mouse survival, despite the tumour's low mutational burden. Conclusion: Integrating mass spectrometry-based immunopeptidomics and whole exome-sequencing is an efficient technique for identifying neoantigenic peptides. A multi-target VLP-based vaccine shows a promising anti-tumour results in an aggressive murine mammary carcinoma cell line. Future clinical application using this strategy is readily feasible and practical, as click-chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection." @default.
• W3157585303 created "2021-05-10" @default.
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• W3157585303 date "2021-04-26" @default.
• W3157585303 modified "2023-10-15" @default.
• W3157585303 title "Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma" @default.
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• W3157585303 doi "https://doi.org/10.1101/2021.04.24.440778" @default.
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