# Vaccinate against the resistance mutation before it takes over

Source: https://onco.cc/ideas/idea-bio1-resistance-mutation-vaccine/  
OnCo record `idea-bio1-resistance-mutation-vaccine` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- technologies: [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Neoantigen](https://onco.cc/terms/neoantigen/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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