免疫疗法正引领抗肿瘤治疗领域迈向新时代，其中新抗原疫苗作为免疫治疗的先锋力量，正以前所未有的速度推进 其基础研究与临床试验，成果迭出，彰显出广阔的发展前景。本文聚焦于新抗原疫苗领域的最新进展，详细介绍备受瞩目的长肽 疫苗与mRNA疫苗两大亮点。肽疫苗因生产高效、易规模化而受关注，虽存在降解快等限制，但纳米载体等技术可帮助其扬长避 短，目前长肽疫苗在黑色素瘤、脑胶质瘤等多种实体瘤患者中均显示出不错的疗效，纳米化的短肽疫苗也在胃癌辅助治疗中展露 优势。mRNA疫苗因在新冠疫情防控中应用广泛受到关注，其安全性及编码多种抗原的优势使其成为肿瘤疫苗热点，如编码多 个KRAS突变的RNA疫苗在胰腺癌中展现出良好效果。且多项研究表明新抗原疫苗联合免疫检查点抑制剂或过继性细胞治疗 可发挥协同作用，进一步提高疗效。文章深入剖析当前新抗原疫苗在临床转化阶段所面临的诸多挑战，并在此基础上，积极探索 并讨论可能的应对策略，旨在为新抗原疫苗未来的发展方向启迪新思维，开辟新路径。

Immunotherapy is propelling the field of anti-tumor treatment into a new era, with neoantigen vaccine serving as a pioneering force in immunotherapy. These vaccines are advancing their basic research and clinical trials at an unprecedented speed, yielding promising results and demonstrating substantial development potential. This review focuses on the latest progress in neoantigen vaccine research, with detailed introduction to the two major highlights: long peptide vaccines and mRNA vaccines. Peptide vaccines have attracted attention for their efficient production and scalability, though their rapid degradation poses a challenge. Advances in nanocarrier technologies help mitigate this limitation, and long-peptide vaccines have demonstrated promising efficacy in patients with various solid tumors, including melanoma and glioblastoma. Additionally, nanoparticle-based short peptide vaccines have demonstrated advantages in adjuvant gastric cancer therapy. mRNA vaccines, widely recognized for their application in COVID-19, have become a hotspot in cancer vaccine development due to their safety and ability to encode multiple antigens. For example, RNA vaccines encoding various KRAS mutations have shown favorable outcomes in pancreatic cancer. Furthermore, several studies suggest that combining neoantigen vaccines with immune checkpoint inhibitors or adoptive cell therapies can exert synergistic effects, further enhancing efficacy. This article delves into the challenges faced by neoantigen vaccines in the clinical translation phase and, based on this, actively explores and discusses potential strategies to address these challenges. The aim is to inspire new ideas and pave the way for future advancements in neoantigen vaccine development.

国家自然科学基金青年项目（No. 82202999）