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

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

## TL;DR

Mutations in the RNA splicing genes SF3B1, SRSF2 and U2AF1 produce the same mis-spliced proteins in patient after patient with MDS, CLL or uveal melanoma. If fragments of those proteins are displayed on common HLA molecules and seen by T cells, one off-the-shelf vaccine or TCR-T therapy could serve every SF3B1-mutant patient instead of being built per person.

## Summary

This idea proposes shared splice-derived neoantigens as off-the-shelf vaccine targets: mutations in the RNA splicing machinery make the same abnormal proteins recur from patient to patient, so one vaccine could serve all who carry the mutation. SF3B1, SRSF2 and U2AF1 mutations produce recurrent mis-spliced transcripts in MDS, CLL and uveal melanoma, some predicted to be HLA-presented, opening the way to Off-the-shelf cancer vaccines or TCR-T cell therapy. The hypothesis is that 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. The test runs from an immunopeptidomic screen using Proteomics & phosphoproteomics to a phase 1 shared vaccine in high-risk SF3B1-mutant MDS.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- 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.
- Proposed test: 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

## Sources

- Kahles et al., Comprehensive analysis of alternative splicing across tumours from 8,705 patients (Cancer Cell 2018): https://doi.org/10.1016/j.ccell.2018.07.001

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/), [Proteomics & phosphoproteomics](https://onco.cc/technologies/proteomics/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/)
- institutions: [Fred Hutchinson Cancer Center](https://onco.cc/institutions/fred-hutch/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [RNA splicing](https://onco.cc/pathways/rna-splicing/)
- terms: [Neoantigen](https://onco.cc/terms/neoantigen/)
- key papers: [Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients](https://onco.cc/key-papers/paper-kahles-cancer-cell/)

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