Zaidi Neeha, Jaffee Elizabeth M, Yarchoan Mark
Johns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Rev Cancer. 2025 May 16. doi: 10.1038/s41568-025-00820-z.
The success of cancer prevention vaccines targeting cancer-causing viruses has drastically reduced cancer mortality worldwide. However, the development of therapeutic cancer vaccines, which aim to elicit an immune response directly against cancer cells, has faced notable clinical setbacks. In this Review, we explore lessons learned from past cancer vaccine trials and how the field has progressed into an era of renewed promise. Previous vaccines primarily targeted tumour-associated antigens and were mainly tested as monotherapies in late-stage cancers. In contrast, contemporary vaccines focus on targeting tumour-specific antigens (neoantigens) and are showing initial evidence of clinical efficacy, particularly in early-stage cancers and precancers when combined with immune checkpoint inhibitors. Advances in tumour profiling and novel vaccine platforms have enhanced vaccine specificity and potency. We discuss recent clinical trials of therapeutic cancer vaccines and outline future directions for the field.
针对致癌病毒的癌症预防疫苗的成功，已在全球范围内大幅降低了癌症死亡率。然而，旨在直接引发针对癌细胞的免疫反应的治疗性癌症疫苗的研发，却遭遇了显著的临床挫折。在本综述中，我们探讨了从过去的癌症疫苗试验中吸取的经验教训，以及该领域如何发展到一个充满新希望的时代。以往的疫苗主要针对肿瘤相关抗原，并且主要在晚期癌症中作为单一疗法进行测试。相比之下，当代疫苗专注于靶向肿瘤特异性抗原（新抗原），并且已初步显示出临床疗效的证据，尤其是在与免疫检查点抑制剂联合使用时，对早期癌症和癌前病变的治疗效果显著。肿瘤分析和新型疫苗平台的进展提高了疫苗的特异性和效力。我们讨论了治疗性癌症疫苗的近期临床试验，并概述了该领域的未来发展方向。
