ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Lymph node macrophages drive innate immune responses to enhance the anti-tumor efficacy of mRNA vaccines.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Rewiring the immune circuit: programming tumor-draining lymph node immunity with nanotechnology.Journal of nanobiotechnology · 2026Review
- Innovative γ-Oryzanol and KC2 Based Lipid Nanoparticles: OryKL Platform Provides Safe and Efficient In Vivo mRNA Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines.Asian journal of pharmaceutical sciences · 2026Review
- Therapeutic mRNA vaccines for lung cancer: reshaping the tumor microenvironment to enhance anti-tumor immunity.Frontiers in immunology · 2026Review
- mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics.Cancer innovation · 2025Review
- mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation.Human vaccines & immunotherapeutics · 2025Review
- Tumor-draining lymph nodes respond to immune checkpoint inhibition and orchestrate tumor immune remodeling.Cancer immunology, immunotherapy : CII · 2025Article
- Positron Emission Tomography-Based Pharmacokinetics of mRNA-Lipid Nanoparticles: A Study Quantifying the ApoE and Macrophage Contribution.ACS applied materials & interfaces · 2025Article
- Lipid Nanoparticles for mRNA Delivery in Cancer Immunotherapy.The AAPS journal · 2025Review
- Article
- Smart Nanoarchitectures for Precision RNA Delivery: Harnessing Endogenous and Exogenous Stimuli in Cancer Treatment.Theranostics · 2025Review
- Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.Molecular cancer · 2024Review
- mRNA vaccines as cancer therapies.Chinese medical journal · 2024Review
- cGAS/STING in skin melanoma: from molecular mechanisms to therapeutics.Cell communication and signaling : CCS · 2024Review
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Immunomodulatory nanoparticles activate cytotoxic T cells for enhancement of the effect of cancer immunotherapy.Nanoscale · 2024Review
- Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.Journal of nanobiotechnology · 2024Review
- Leveraging high-throughput screening technologies in targeted mRNA delivery.Materials today. Bio · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mRNA vaccines are promising for cancer treatment. Efficient delivery of mRNAs encoding tumor antigens to antigen-presenting cells (APCs) is critical to elicit anti-tumor immunity. Herein, we identified a novel lipid nanoparticle (LNP) formulation, L17-F05, for mRNA vaccines by screening 34 ionizable lipids and 28 LNP formulations using human primary APCs. Subcutaneous delivery of L17-F05 mRNA vaccine encoding Gp100 and Trp2 inhibited tumor growth and prolonged the survival of mice bearing B16F10 melanoma. L17-F05 efficiently delivered mRNAs to conventional dendritic cells (cDCs) and macrophages in draining lymph nodes (dLNs). cDCs functioned as the main APCs by presenting antigens along with enhanced expression of co-stimulatory molecules. Macrophages triggered innate immune responses centered on type-I interferon (IFN-I) in dLNs. Lymph node (LN) macrophage depletion attenuated APC maturation and anti-tumor activity of L17-F05 mRNA vaccines. Loss-of-function studies revealed that L17-F05 works as a self-adjuvant by activating the stimulator of interferon genes (STING) pathway in macrophages. Collectively, the self-adjuvanticity of L17-F05 triggered innate immune responses in LN macrophages via the STING-IFN-I pathway, contributing to APC maturation and potent anti-tumor activity of L17-F05 mRNA vaccines. Our findings provide strategies for further optimization of mRNA vaccines based on the innate immune response driven by LN macrophages.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.