A Translational Framework for a Hybrid mRNA Vaccine Targeting Glioblastoma

Integrating Innate Priming, Personalized Neoantigens, and Blood–Brain Barrier Penetrating Delivery

Repository Description: A theoretical framework proposing a hybrid mRNA vaccine strategy for Glioblastoma (GBM). It integrates innate immune priming, personalized neoantigens, and focused ultrasound (FUS) for blood-brain barrier (BBB) penetration to overcome immunoresistance.

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Author Information

Collin B. George, BS

• Affiliation: University of Washington Medical Center (Pre-medical Research)
• Contact: [email protected]
• ORCID: 0009-0007-8162-6839

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Project Metadata

Attribute	Details
Repository Initialization	November 25, 2025
Document Type	Narrative Review and Translational Framework
Status	Pre-print / Manuscript Under Preparation
Keywords	glioblastoma; mRNA vaccine; blood-brain barrier; neoantigens; focused ultrasound; immunotherapy; IL-12; RIG-I ligands

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Abstract

Glioblastoma (GBM) remains lethal despite multimodal therapy, with median survival under 15 months. Immunotherapy has failed in over 100 clinical trials due to three fundamental barriers: inadequate immune priming in "cold" tumors, blood–brain barrier (BBB) exclusion of therapeutics, and profound local immunosuppression.

We present a translational framework for a hybrid mRNA vaccine that addresses all three barriers simultaneously:

1. Innate Priming: Universal innate immune primers (poly(I:C)/RIG-I ligands, IL-12) activate dendritic cells
2. Adaptive Targeting: Patient-specific neoantigen mRNA drives tumor-targeted T-cell responses
3. BBB Penetration: Peptide-modified lipid nanoparticles or focused ultrasound-guided delivery

Timed checkpoint blockade exploits vaccine-induced PD-L1 upregulation to unleash infiltrating T cells.

Validation Strategy

We propose stepwise validation:

• Computational modeling to optimize dosing
• In-vitro co-cultures to confirm antigen presentation
• Patient-derived xenografts to demonstrate BBB crossing and tumor control
• Phase I trial using post-resection focused ultrasound delivery with PET and ctDNA endpoints

This approach aligns with current two-week manufacturing timelines and offers a modular strategy to convert GBM from immunologically cold to responsive.

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Repository Contents

.
├── main.tex              # Primary LaTeX source file
├── references.bib        # BibTeX citation database (2024-2025 focus)
├── figures/              # TikZ/PGFPlots source code and generated diagrams
│   ├── figure1_bbb.tex
│   ├── figure2_mechanism.tex
│   └── figure3_validation.tex
└── README.md             # This file

File Descriptions

• main.tex: The primary LaTeX manuscript configured for standard academic document classes
• references.bib: BibTeX database with citations from clinical trials and translational studies (2024–2025)
• figures/: Source code (TikZ/PGFPlots) and generated assets for manuscript diagrams

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Compilation Instructions

This manuscript is written in LaTeX. To compile the PDF from source, a standard TeX distribution is required.

Requirements

• TeX Distribution: TeX Live, MacTeX, or MiKTeX
• LaTeX Packages:
  • geometry, amsmath, siunitx, booktabs
  • graphicx, tikz, pgfplots
  • enumitem, lineno, natbib, hyperref

Build Commands

Using latexmk (Recommended)

latexmk -pdf -pvc main.tex

Manual Compilation

pdflatex main.tex
bibtex main
pdflatex main.tex
pdflatex main.tex

Overleaf

1. Upload all files to a new Overleaf project
2. Set compiler to pdfLaTeX
3. Compile normally

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Citation Information

To cite this repository or the draft manuscript:

BibTeX

@misc{George2025GBM,
  author       = {George, Collin B.},
  title        = {A Translational Framework for a Hybrid mRNA Vaccine Targeting Glioblastoma: 
                  Integrating Innate Priming, Personalized Neoantigens, and 
                  Blood--Brain Barrier Penetrating Delivery},
  year         = {2025},
  month        = {November},
  note         = {Pre-print repository},
  howpublished = {\url{https://github.com/[USERNAME]/gbm-hybrid-mrna-framework}},
  doi          = {[DOI if available]}
}

APA Format

George, C. B. (2025). A translational framework for a hybrid mRNA vaccine targeting 
glioblastoma: Integrating innate priming, personalized neoantigens, and blood-brain 
barrier penetrating delivery [Manuscript in preparation]. University of Washington 
Medical Center. https://github.com/[USERNAME]/gbm-hybrid-mrna-framework

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Disclaimer

This independent narrative review was conducted as part of premedical research and does not represent the views of UW Medicine.

• No external funding was received for this conceptual framework
• No conflicts of interest declared
• No patents or proprietary technologies claimed

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License

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

You are free to:

• Share — copy and redistribute the material in any medium or format
• Adapt — remix, transform, and build upon the material for any purpose, even commercially

Under the following terms:

• Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made

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Related Resources

• ORCID Profile: 0009-0007-8162-6839
• Contact: [email protected]

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Project Status

• Manuscript drafted
• Figures generated (TikZ/inline)
• Peer review submission
• Pre-print publication
• Journal submission

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Acknowledgments

The author thanks mentors and colleagues at UW Medicine for valuable discussions on translational immunotherapy, focused ultrasound applications in neuro-oncology, and mRNA vaccine development. Special appreciation to the GBM research community for openly sharing clinical trial data and preclinical insights that informed this framework.

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Last Updated: November 25, 2025
Repository Version: 1.0.0