OnCo
ideasIdea

What makes a neoantigen actually immunogenic?

Vaccines can now encode dozens of a tumour's mutations, but only a minority provoke useful T cells. Learning the rules would make vaccines smaller, cheaper, and stronger.

Current prediction relies on HLA binding and expression; immunogenicity also depends on TCR repertoire, dissimilarity to self, clonality, and presentation by dendritic cells. Long-term vaccine responders (Balachandran pancreatic cohort) provide ground truth.

Hypothesis
Immunogenic neoantigens can be predicted with >50% precision by models trained on validated T-cell responses from vaccine trials, cutting the number of epitopes needed per vaccine from 34 to under 10.
Rationale
INTerpath-001 success and autogene cevumeran follow-up supply immune-monitoring data; TCR-sequencing and antigen-specific assays are scalable.
What would test it
Pooled analysis of vaccine-trial immunomonitoring to train and prospectively validate an immunogenicity model; then a randomised trial of model-selected 10-epitope vs standard 34-epitope vaccines with T-cell response as primary endpoint.
Maturity
preclinical evidence

Connected

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Pages like this

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technologies

2
Personalised neoantigen (mRNA) vaccinesTCR-T cell therapy

drugs

2
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene

institutions

3
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NIH)Siteman Cancer Center, Washington University

pathways

1
Antigen presentation & immune editing

terms

1
Neoantigen