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Spliced to kill: RNA mis-splicing derived cancer neoantigens

Anurag V Prabhu1, Carla Azar-Koussa1, Zahava Siegfried1

  • 1Department of Biochemistry and Molecular Biology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Trends in Cancer
|June 20, 2025
PubMed

Insights

Researchers identified novel cancer neoantigens from splicing factor mutations in myeloid cancers. These findings open new avenues for targeted cancer therapies, including engineered T cell treatments and vaccines.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Identifying shared cancer-specific neoantigens is crucial for effective neoantigen-based cancer therapies.
  • Splicing factor mutations are prevalent in certain myeloid malignancies, but their role in neoantigen generation is not well understood.

Purpose of the Study:

  • To investigate novel sources of cancer neoantigens in splicing factor mutant myeloid malignancies.
  • To explore the potential of these neoantigens for developing advanced cancer immunotherapies.

Main Methods:

  • Analysis of tumor samples from patients with splicing factor mutant myeloid malignancies.
  • Identification and characterization of neoantigens arising from aberrant splicing events.
  • Assessment of neoantigen presentation and potential immunogenicity.

Main Results:

  • Discovery of a novel class of cancer neoantigens generated by aberrant splicing in myeloid malignancies.
  • Demonstration that these mis-spliced neoantigens can be recognized by the immune system.
  • Identification of specific neoantigens shared across patients with similar mutations.

Conclusions:

  • Aberrantly spliced neoantigens represent a promising, previously unrecognized source for cancer immunotherapy.
  • Engineered T cell receptor (TCR)-T cell therapies and neoantigen-based vaccines targeting these novel neoantigens hold significant therapeutic potential.
  • This discovery advances the field of personalized cancer medicine by expanding the repertoire of actionable neoantigens.
Keywords:
CAR-TRNA processingRNA splicingimmunotherapyneoantigens

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