ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Type I Interferons Interfere with the Capacity of mRNA Lipoplex Vaccines to Elicit Cytolytic T Cell Responses.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 122 citations in OpenAlex.
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
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- Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Eliciting antitumor immunity via therapeutic cancer vaccines.Cellular & molecular immunology · 2025Review
- Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport.NPJ vaccines · 2025Article
- Cancer vaccines: current status and future directions.Journal of hematology & oncology · 2025Review
- The mRNA component of LNP-mRNA vaccines triggers IFNAR-dependent immune activation which attenuates the adaptive immune response.Frontiers in immunology · 2025Article
- mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy.Biomarker research · 2024Review
- Molecular Dynamics Simulation of Lipid Nanoparticles Encapsulating mRNA.Molecules (Basel, Switzerland) · 2024Article
- β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model.Bioactive materials · 2024Article
- Immunogenicity of concomitant SARS-CoV-2 and influenza vaccination in UK healthcare workers: a prospective longitudinal observational study.The Lancet regional health. Europe · 2024Article
- Feasibility of Using a Type I IFN-Based Non-Animal Approach to Predict Vaccine Efficacy and Safety Profiles.Vaccines · 2024Review
- mRNA vaccine designs for optimal adjuvanticity and delivery.RNA biology · 2024Review
- Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens.Fundamental research · 2023Review
- An Ionizable Lipid Material with a Vitamin E Scaffold as an mRNA Vaccine Platform for Efficient Cytotoxic T Cell Responses.ACS nano · 2023Article
- The use of RNA-based treatments in the field of cancer immunotherapy.Molecular cancer · 2023Review
- Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial.The Lancet regional health. Europe · 2023Article
- Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines.Biomedicines · 2023Review
- Neoantigens: promising targets for cancer therapy.Signal transduction and targeted therapy · 2023Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given their high potential to evoke cytolytic T cell responses, tumor antigen-encoding messenger RNA (mRNA) vaccines are now being intensively explored as therapeutic cancer vaccines. mRNA vaccines clearly benefit from wrapping the mRNA into nano-sized carriers such as lipoplexes that protect the mRNA from degradation and increase its uptake by dendritic cells in vivo. Nevertheless, the early innate host factors that regulate the induction of cytolytic T cells to mRNA lipoplex vaccines have remained unresolved. Here, we demonstrate that mRNA lipoplexes induce a potent type I interferon (IFN) response upon subcutaneous, intradermal and intranodal injection. Regardless of the route of immunization applied, these type I IFNs interfered with the generation of potent cytolytic T cell responses. Most importantly, blocking type I IFN signaling at the site of immunization through the use of an IFNAR blocking antibody greatly enhanced the prophylactic and therapeutic antitumor efficacy of mRNA lipoplexes in the highly aggressive B16 melanoma model. As type I IFN induction appears to be inherent to the mRNA itself rather than to unique properties of the mRNA lipoplex formulation, preventing type I IFN induction and/or IFNAR signaling at the site of immunization might constitute a widely applicable strategy to improve the potency of mRNA vaccination.
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