OnCo
ideasIdea

Vaccines aimed only at mutations shared by every tumour cell

Personal cancer vaccines target many mutations, some of which are present in only part of the tumour. Aiming only at mutations every cell shares should stop the tumour escaping by losing them.

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.

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.
What would test it
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
Who has to act
industry
Cost to try
Large (over $50M)
Years to first evidence
5
Bottlenecks it attacks

Key papers

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translationalNew England Journal of Medicine 2017
TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse

Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.

Connected

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Pages like this

not linked directly; found by shared links

technologies

2
Personalised neoantigen (mRNA) vaccinesTIL therapy

companies

2
BioNTechModerna

terms

1
Neoantigen

trials

1
INTerpath-001 (V940-001)

bottlenecks

2
No one can predict who responds to immunotherapyTumour heterogeneity and clonal evolution

key papers

1
TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse