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
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.