# A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval

Source: https://onco.cc/ideas/idea-moon-lynch-vaccine-phase3/  
OnCo record `idea-moon-lynch-vaccine-phase3` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

People with Lynch syndrome have a very high lifetime cancer risk from a predictable set of mutations. Vaccinate them against those shared mutations before cancer appears.

## Summary

Mismatch repair deficiency produces recurrent frameshift neoantigens shared across Lynch-associated tumours, and pilot vaccines have shown immunogenicity in carriers and in mice reduced tumour incidence. The proposal is to take a multi-epitope frameshift vaccine (mRNA or viral vector, possibly with a checkpoint-sparing adjuvant) into a randomised prevention trial in carriers with a surrogate endpoint of adenoma and early-cancer incidence at colonoscopy, positioning it as the first preventive cancer vaccine registration for a hereditary syndrome.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Vaccination reduces incident advanced adenomas and cancers in Lynch carriers by at least 40% over five years compared with surveillance alone.
- Rationale: Predictable shared antigens, a defined high-risk population with regular endoscopic surveillance providing a fast surrogate, and mature vaccine platforms make this the most tractable preventive vaccine in oncology.
- Proposed test: Phase 2b/3 randomised placebo-controlled trial in about 1,500 carriers with colonoscopy-based endpoints; interim immunological and adenoma readouts at two years.
- Maturity: early-clinical
- Actor: research

## Sources

- Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017): https://doi.org/10.1200/JCO.2017.73.6314

## Connected records

- ideas: [Cancer interception vaccines for high-risk carriers](https://onco.cc/ideas/idea-interception-vaccines/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Mismatch-repair-deficient endometrial cancer](https://onco.cc/cancers/endometrial-mmr-deficient/)
- technologies: [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/)
- terms: [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Neoantigen](https://onco.cc/terms/neoantigen/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/), [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/)
- key papers: [First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers](https://onco.cc/key-papers/paper-lynch-frameshift-vaccine-ccr-2020/), [National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer](https://onco.cc/key-papers/paper-childers-j-clin-oncol/)
- roadmaps: [Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers](https://onco.cc/roadmaps/prevention-roadmap/)

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