Oncogene Mutations: The Shared Antigen Vaccines That Work?

Paredes, Rodrigo; Haldar, S Daniel; Pant, Shubham; O'Reilly, Eileen M · Annu Rev Med · 2026

review · Level V

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Abstract

Cancer immunotherapy has advanced through immune checkpoint inhibitors and T cell therapies, yet challenges persist in overcoming immune evasion. Neoantigen-based vaccines have shown promise, particularly in tumors with high tumor mutation burden. However, logistical barriers and tumor heterogeneity limit their scalability. Shared oncogenic driver mutations (e.g., <i>KRAS</i>, <i>EGFR</i>, <i>IDH</i>) offer a stable and broadly applicable alternative. Clinical trials demonstrate their immunogenicity and potential in minimal residual disease settings. Advances in vaccine delivery and immune modulation, including adjuvants and cytokine-based therapies, may further enhance efficacy. This review explores the evolution of oncogene-directed vaccines, their clinical impact, and future strategies to optimize their therapeutic potential.

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