ArticleScience advances2025
Large-scale transcript variants dictate neoepitopes for cancer immunotherapy.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Current landscape and future directions of neoantigen vaccines: A new era of personalized cancer immunotherapy.Innovation (Cambridge (Mass.)) · 2026Review
- Cancer Vaccine Development: Toward Artificial Intelligence-Assisted Personalized Cell Membrane Nanovaccine.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Review
- Targeting non-canonical antigens unlocks functional T-cell responses in renal cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Research on the Mechanism of "Cold Tumor" Formation and Immunotherapy for Its Transformation into "Hot Tumor".Oncology research · 2026Review
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- TRANSAID: a hybrid deep learning framework for translation site prediction with integrated biological feature scoring.Frontiers in bioinformatics · 2025Article
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Authors and funding
16 authors.
Funding
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Abstract
Precise neoepitope discovery is crucial for effective cancer therapeutic vaccines. Conventional approaches struggle to build a repertoire with sufficient immunogenic epitopes. We developed a workflow leveraging full-length ribosome-nascent chain complex-bound mRNA sequencing (FL-RNC seq) and artificial intelligence-based predictive models to accurately identify the neoepitope landscape, especially large-scale transcript variants (LSTVs) missed by short-read sequencing. In the MC38 mouse model, we identified 22 LSTV-derived neoepitopes encoded by a synthesized mRNA lipid nanoparticle vaccine. As a standalone therapy and combined with anti-PD-1 immunotherapy, the vaccine curbed tumor progression, induced robust T cell-specific immunity, and modulated the tumor microenvironment. This underscores the multifaceted potentials of LSTV-derived vaccines. Our approach expands the neoepitope source repertoire, offering a method for discovering personalized cancer vaccines applicable to a broader tumor range. The results highlight the importance of comprehensive neoepitope identification and the promise of LSTV-based vaccines for cancer immunotherapy.
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Registered trials
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