{"entity":{"id":"idea-moon-lynch-vaccine-phase3","kind":"idea","name":"A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["idea-interception-vaccines"],"cancers":["colorectal","endometrial"],"sections":[],"technologies":["shared-antigen-vaccine","neoantigen-mrna-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","neoantigen"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"large","horizonYears":8},"route":"/ideas/idea-moon-lynch-vaccine-phase3/","neighbours":{"idea":[{"id":"idea-interception-vaccines","kind":"idea","name":"Cancer interception vaccines for high-risk carriers","route":"/ideas/idea-interception-vaccines/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"}],"technology":[{"id":"shared-antigen-vaccine","kind":"technology","name":"Off-the-shelf cancer vaccines","route":"/technologies/shared-antigen-vaccine/"},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"}],"bottleneck":[{"id":"b-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"},{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"}],"paper":[{"id":"paper-lynch-frameshift-vaccine-ccr-2020","kind":"paper","name":"First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers","route":"/key-papers/paper-lynch-frameshift-vaccine-ccr-2020/"},{"id":"paper-childers-j-clin-oncol","kind":"paper","name":"National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer","route":"/key-papers/paper-childers-j-clin-oncol/"}],"roadmap":[{"id":"prevention-roadmap","kind":"roadmap","name":"Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers","route":"/roadmaps/prevention-roadmap/"}]}}