Current landscape and future directions of neoantigen vaccines: A new era of personalized cancer immunotherapy

Public summary

* Neoantigens are tumor-specific and highly immunogenic targets for personalized cancer immunotherapy.

* Artificial intelligence (AI) improves neoantigen prediction, yet challenges remain in accuracy.

* Diverse vaccine platforms show promise in clinical trials.

* Combination therapies are crucial for enhancing antitumor efficacy of neoantigen vaccines.

Abstract

At the forefront of cancer immunotherapy, neoantigens are tumor specific and highly immunogenic, and they have emerged as the key target for personalized oncology. Neoantigen vaccines have demonstrated promising immunologic responses and survival benefit in clinical trials with the combination of chemoradiotherapy and immune checkpoint therapy. This review provides a comprehensive synthesis of biological mechanisms and the next-generation screening approach of cancer neoantigens. We evaluate the current vaccine platforms and the design and vector of cancer neoantigen vaccines, and we additionally analyze strategies to overcome immunosuppressive tumor microenvironment challenges. We conducted a detailed analysis of ongoing and preliminary neoantigen vaccine clinical trials, summarizing existing challenges and areas requiring further improvement. Through an in-depth analysis of the latest research advances, we propose current optimization strategies for neoantigen vaccines, including novel screening models and innovative delivery approaches. Future directions for personalized cancer immunotherapy are outlined, with neoantigen vaccines positioned as pivotal enabling platforms.