# Evaluating neoantigen-vaccine responses through mechanistic and model-based frameworks

Article · Ibrahim EIK, Laurén I, Veerman RE, Jönsson S, Ytterberg AJ, Lindqvist A, Mangsbo SM, Friberg LE

- Archive id: doi:10.1038/s41698-026-01579-8
- Published: 2026-06-24
- Venue: NPJ precision oncology
- DOI: https://doi.org/10.1038/s41698-026-01579-8
- PMID: 42342810
- PMCID: PMC13294367
- Citations: 0
- Source URL: https://doi.org/10.1038/s41698-026-01579-8
- PDF: https://europepmc.org/articles/PMC13294367/pdf
- Provenance: europepmc

## Abstract

Therapeutic cancer vaccines activate tumor-specific T-cells to reduce tumor burden, yet face challenges when integrating and translating multi-level complex preclinical data into actionable insights. We present a model-based framework to integrate diverse preclinical data, comparing synthetic long peptide vaccines with or without adjuvant stimuli to a vaccine-drug conjugate approach by Adaptable Drug Affinity Conjugate technology. This technology provides modular and rapid conjugate formation via high-affinity binding between a peptide-tagged vaccine antigen and a CD40-targeting antibody, acting as an adjuvant and delivery vehicle. Our developed semi-mechanistic modelling framework successfully linked dosing to tumor dynamics, incorporating four sub-models: pharmacokinetic, peptide uptake by antigen-presenting cells, T-cell response, and tumor growth in TC-1 and MC38 tumors. Model-based simulations highlighted the importance of affinity conjugation on pharmacokinetics and efficacy. Effector T-cells mediated tumor shrinkage. Antibody dose-dependent effects were identified and quantified in the immune-responsive MC38 model. This framework supports rational vaccine optimization and translational decision-making. The graphical abstract was created in https://BioRender.com .

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

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