Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma.

Details

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UNIL restricted access
State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_C41D094CADC7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma.
Journal
Journal for immunotherapy of cancer
Author(s)
Mohsen M.O., Speiser D.E., Michaux J., Pak H., Stevenson B.J., Vogel M., Inchakalody V.P., de Brot S., Dermime S., Coukos G., Bassani-Sternberg M., Bachmann M.F.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
01/2022
Peer-reviewed
Oui
Volume
10
Number
1
Pages
e002927
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Harnessing the immune system to purposely recognize and destroy tumors represents a significant breakthrough in clinical oncology. Non-synonymous 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 multitarget vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform.
Mutations of murine mammary carcinoma cells were identified 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.
As compared with short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells, which readily produced interferon gamma (IFN-γ) and tumor-necrosis factor α (TNF-α). The resulting anti-tumor effect was associated with favorable immune re-polarization in the tumor microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumor recurrence and metastases, and prolonged mouse survival, despite the tumor's low mutational burden.
Integrating mass spectrometry-based immunopeptidomics and whole exome sequencing is an efficient approach for identifying neoantigenic peptides. Our multitarget VLP-based vaccine shows a promising anti-tumor effect in an aggressive murine mammary carcinoma model. 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.
Keywords
Animals, Antigens, Neoplasm/therapeutic use, Breast Neoplasms/drug therapy, Cancer Vaccines/immunology, Cell Line, Tumor, Female, Humans, Immunotherapy/methods, Mice, Precision Medicine/methods, breast neoplasms, immunotherapy, vaccination
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2022 9:55
Last modification date
29/07/2022 6:38
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