Blog

Marco Donia: RNA splicing generates cancer neoantigens, beyond mutations

Marco Donia/dff.dk

Mar 3, 2025, 10:57

Marco Donia: RNA splicing generates cancer neoantigens, beyond mutations

Marco Donia, Associate Professor in Clinical Oncology at the University of Copenhagen, shared a post on LinkedIn:

“RNA Splicing Generates Cancer Neoantigens, beyond mutations. (Darwin K. et al., Nature Magazine, 19 Feb 2025).

RNA splicing aberrations generate neoantigens, presenting new targets for cancer immunotherapy. These findings expand antigen discovery beyond somatic mutations, with potential applications in T-cell-based therapies and cancer vaccines.

Key Findings:

Identified cancer-specific antigens arising from RNA splicing aberrations across multiple tumor types.
High intratumoral conservation for most of these antigens (e.g., GNAS neojunction in glioma, mesothelioma, prostate cancer and liver cancer).
Immunotherapeutic potential: these NEJ*-derived neontigens are processed, presented, and can be recognized by cytotoxic T cells.

Take-Home Messages:

Aberrant splicing is an underexplored source of tumor-specific antigens.
Neoantigens from aberrant splicing generally have low intratumor heterogeneity, potentially enabling effective targeting of all tumor cells.

Clinical Implications:

May expand immunotherapy targets for tumors with low mutational burden or high intratumor heterogeneity.
Increases potential for TCR-based therapies and cancer vaccines.
Highlights the critical role of transcriptomics (RNA-seq) in immunotherapy design.

Outstanding work from the teams of Christopher A. Klebanoff, M.D., Joe Costello and Hideho Okada (corresponding authors).

NEJ: neoepitope encoding neo-junctions. Neo-junctions are cancer-specific splicing events (more).”

cancer Cancer Neoantigens Christopher A. Klebanoff clinical oncology Darwin K. fight against cancer Global fight against cancer Hideho Okada immunotherapy Joe Costello liver cancer Marco Donia Nature Magazine OncoDaily Oncology prostate cancer RNA Splicing University of Copenhagen

Beyond the Red Carpet: Oscar Winners and Nominees Who Fought Cancer

Oncologist Near Me – Lidia Schapira: A Leader in Cancer Care and Medical Education

Dr. Manette Le Grange joins OncoDaily Editorial Board

FDA Grants Priority Review to Merck’s Application for KEYTRUDA® (pembrolizumab) Plus Standard of Care as Perioperative Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

New Paper Alert Real-Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON-2 Retrospective Experience