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Shared splice-derived neoantigens as off-the-shelf vaccine targets

Mutations in the cell's editing machinery make recurrent abnormal proteins across many patients. If those are visible to T cells, one vaccine could serve many people instead of being built per patient.

SF3B1, SRSF2, and U2AF1 mutations produce recurrent mis-spliced transcripts (MDS, CLL, uveal melanoma); some are predicted to be presented on HLA; recurrence across patients would allow off-the-shelf vaccines or TCR-T.

Hypothesis
Recurrent splice-junction neoantigens from SF3B1-mutant cells are presented on common HLA alleles and elicit T-cell responses, enabling a shared vaccine for SF3B1-mutant MDS and CLL.
Rationale
Immunopeptidomics has detected splice-derived peptides; SF3B1 K700E is recurrent; shared-antigen platforms (KRAS vaccines, PRAME TCR) prove the model.
What would test it
Immunopeptidomic screen of SF3B1-mutant primary cells for HLA-presented splice peptides, T-cell reactivity assays in patients, then a phase 1 shared vaccine in high-risk SF3B1-mutant MDS.
Maturity
speculative

Connected

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cancers

3
Acute myeloid leukaemiaChronic lymphocytic leukaemiaMelanoma

technologies

3
Off-the-shelf cancer vaccinesProteomics & phosphoproteomicsTCR-T cell therapy

institutions

2
Fred Hutchinson Cancer CenterMemorial Sloan Kettering Cancer Center

pathways

2
Antigen presentation & immune editingRNA splicing

terms

1
Neoantigen