# Vaccines aimed only at mutations shared by every tumour cell

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

## TL;DR

Personal cancer vaccines target a list of mutations, some present in only part of the tumour, so the tumour can escape by losing them. Restricting vaccines and T-cell products to clonal mutations shared by every tumour cell, identified by multi-region sequencing, should close that escape route.

## Summary

Clonal (truncal) neoantigens are present in all tumour cells, so an immune response to them cannot be escaped by subclonal antigen loss. Multi-region sequencing or high-purity clonality inference can identify them. Personalised mRNA vaccines and clonal-neoantigen-reactive T-cell products (such as those pioneered from TRACERx data) could be restricted to clonal targets and compared with unselected designs.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Vaccines or T-cell products restricted to clonal neoantigens produce fewer antigen-loss relapses and longer disease-free survival than products built from unselected neoantigen lists of equal size.
- Rationale: Clonal neoantigen burden, not total burden, predicted checkpoint inhibitor response in lung and melanoma cohorts; escape by loss of subclonal antigens is a documented failure mode.
- Proposed test: Randomised phase 2 in the adjuvant setting comparing clonal-restricted versus standard neoantigen selection with the same vaccine platform; endpoint recurrence-free survival and antigen-loss at relapse.
- Maturity: early-clinical
- Actor: industry

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- technologies: [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [TIL therapy](https://onco.cc/technologies/til-therapy/)
- companies: [BioNTech](https://onco.cc/companies/biontech/), [Moderna](https://onco.cc/companies/moderna/)
- terms: [Neoantigen](https://onco.cc/terms/neoantigen/)
- trials: [INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- key papers: [TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse](https://onco.cc/key-papers/paper-tracerx-100-nejm-2017/)

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