{"entity":{"id":"idea-bio1-resistance-mutation-vaccine","kind":"idea","name":"Vaccinate against the resistance mutation before it takes over","aka":[],"tldr":"Resistance often arrives as the same few mutations. Teaching the immune system to recognise them in advance could remove the escaping cells while they are still rare.","summary":"Recurrent resistance alleles such as EGFR T790M, ESR1 hotspot mutations and KRAS secondary mutations create new peptides, absent from normal cells, that may be presented on MHC. An off-the-shelf vaccine or T-cell product against a small set of public resistance neoantigens, given at the start of or during targeted therapy, would apply immune pressure precisely to the cells that are expanding under drug pressure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["shared-antigen-vaccine","neoantigen-mrna-vaccine"],"targets":["egfr","estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neoantigen","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination against a recurrent resistance neoantigen generates detectable specific T cells and reduces the emergence of that allele in plasma during targeted therapy.","rationale":"Public resistance mutations are shared across many patients, which makes an off-the-shelf product feasible; targeting a clone while it is rare is when immune clearance is most plausible.","test":"Immunogenicity and pharmacodynamic study in patients on osimertinib or an oral SERD, comparing allele emergence rates in plasma between vaccinated and control groups.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio1-resistance-mutation-vaccine/","neighbours":{"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/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}