Oncogene Mutations: The Shared Antigen Vaccines That Work?

This review discusses the rationale and current status of vaccines targeting shared oncogenic driver mutations as a cancer immunotherapy strategy.

Key points:

• Traditional cancer immunotherapies—checkpoint inhibitors and T‑cell therapies—are effective but limited by tumor immune evasion.
• Neoantigen vaccines have shown benefit, especially in tumors with high mutation burden, but are constrained by patient-specific design, manufacturing complexity, and intratumoral heterogeneity.
• Vaccines directed against recurrent, shared oncogenic drivers such as KRAS, EGFR, and IDH offer a more stable, broadly applicable target set compared with individualized neoantigens.
• Early clinical data indicate these oncogene-directed vaccines are immunogenic and may be particularly useful in settings of minimal residual disease, where tumor burden and immune suppression are lower.
• The review highlights emerging strategies to improve these vaccines, including optimized delivery platforms, potent adjuvants, and combination approaches with cytokine-based therapies and other immune modulators.
• Overall, oncogene-directed vaccination is presented as a promising, scalable complement to existing immunotherapies, with ongoing efforts focused on enhancing response rates and durability.