ArticleGastroenterology2021
Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 109 citations in OpenAlex.
- Distinct mutational landscapes for germline and somatic cancer variants in forty tumor suppressor genes.American journal of human genetics · 2026Article
- Mechanism of neoantigen generation and advances in neoantigen-based immunotherapies in colorectal cancer.Medical oncology (Northwood, London, England) · 2026Review
- Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Vaccine strategies for cancer prevention in Lynch syndrome: the potential of dendritic cell-based therapy.Familial cancer · 2026Review
- Prevention strategies for hereditary gynaecological cancer in Lynch syndrome.Familial cancer · 2026Review
- Distinct mutational landscapes when comparing germline and somatic cancer variants in forty tumor suppressor genes.bioRxiv : the preprint server for biology · 2026Article
- Review
- Mechanistic biomarkers for cancer vaccine development: from cancer cell biology to neoantigen-guided precision immunotherapy.Frontiers in cell and developmental biology · 2026Review
- Epigenetic and transcriptomic analysis revealed ceRNA regulatory network in glioblastoma multiforme.European journal of medical research · 2025Article
- Targeting neoantigens conserved across organs and species overcomes tumor immune escape.bioRxiv : the preprint server for biology · 2025Article
- The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives.Journal of hematology & oncology · 2025Review
- Segmental versus Extended Resection for Colon Cancer in Lynch Syndrome.Clinics in colon and rectal surgery · 2025Review
- Inherited Susceptibility to Cancer: Past, Present and Future.Annals of human genetics · 2025Review
- A frameshift-generated cancer neoepitope that controls tumor burden in prophylaxis as well as therapy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immunoprevention of non-viral cancers: challenges and strategies for early intervention.Cancer cell international · 2025Review
- Discovery and validation of frameshift-derived neopeptides in Lynch syndrome: paving the way for novel cancer prevention strategies.Journal for immunotherapy of cancer · 2025Article
- Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application.Cell death & disease · 2025Review
- SITC strategic vision: prevention, premalignant immunity, host and environmental factors.Journal for immunotherapy of cancer · 2025Review
- Tumour mutational burden using a targeted panel approach for comprehensive tumour profiling focusing on colorectal cancer.Hereditary cancer in clinical practice · 2025Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection.2021
Authors and funding
28 authors at 9 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsDNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated.
methodsA genome-wide database of 488,235 mouse coding mononucleotide repeats was established, from which a set of candidates was selected based on repeat length, gene expression, and mutation frequency. In silico prediction, in vivo immunogenicity testing, and epitope mapping was used to identify candidates for FSP vaccination.
resultsWe identified 4 shared FSP neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) that induced CD4/CD8 T cell responses in naïve C57BL/6 mice. Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival. Combination of FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival even more effectively than FSP vaccination alone.
conclusionsOur preclinical findings support a clinical strategy of recurrent FSP neoantigen vaccination for LS cancer immunoprevention.
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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.