A synthetic DNA template for fast manufacturing of versatile single epitope mRNA.
MT: Oligonucleotides: Therapies and Applications
T cell
cancer
mRNA
neoantigen
synthetic DNA template
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
13 Sep 2022
13 Sep 2022
Historique:
received:
04
05
2022
accepted:
14
08
2022
entrez:
26
9
2022
pubmed:
27
9
2022
medline:
27
9
2022
Statut:
epublish
Résumé
A flexible, affordable, and rapid vaccine platform is necessary to unlock the potential of personalized cancer vaccines in order to achieve full clinical efficiency. mRNA cancer vaccine manufacture relies on the rigid sequence design of multiepitope constructs produced by laborious bacterial cloning and time-consuming plasmid preparation. Here, we introduce a synthetic DNA template (SDT) assembly process, which allows cost- and time-efficient manufacturing of single (neo)epitope mRNA. We benchmarked SDT-derived mRNA against mRNA derived from a plasmid DNA template (PDT), showing that monocyte-derived dendritic cells (moDCs) electroporated with SDT-mRNA or PDT-mRNA, encoding HLA-I- or HLA-II-restricted (neo)epitopes, equally activated T cells that were modified to express the cognate T cell receptors. Furthermore, we validated the SDT-mRNA platform for neoepitope immunogenicity screening using the characterized HLA-A2-restricted neoepitope DHX40B and four new candidate HLA-A2-restricted melanoma neoepitopes. Finally, we compared SDT-mRNA with PDT-mRNA for vaccine development purposes. moDCs electroporated with mRNA encoding the HLA-A2-restricted, mutated Melan-A/Mart-1 epitope together with TriMix mRNA-generated high levels of functional Melan-A/Mart-1-specific CD8
Identifiants
pubmed: 36159589
doi: 10.1016/j.omtn.2022.08.021
pii: S2162-2531(22)00220-7
pmc: PMC9464653
doi:
Types de publication
Journal Article
Langues
eng
Pagination
943-954Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The use of dendritic cells electroporated with tumor antigen and TriMix mRNA is the topic of a patent (WO2009/034172) on which K.T. is filed as an inventor. This patent is licensed to eTheRNA Immunotherapies NV. The synthetic DNA template for in vitro mRNA transcription is listed under patent application WO2021/185833 on which K.T., L.F., and C.B. are listed as inventors. L.P., B.F., L.L., and C.B. are employees and shareholders at myNEO NV, a company developing neoantigen immunotherapies. The prediction pipeline used for the identification of patient-specific neoantigens is the topic of two patents (NeoMS:EP20185779.4 and NeoIM:EP20202140.8) belonging to myNEO NV.
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