Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Cancer Cell. 2024 Jul 8;42(7):1163-1184. doi: 10.1016/j.ccell.2024.05.005. Epub 2024 Jun 6.
Vaccines are the most impactful medicines to improve health. Though potent against pathogens, vaccines for cancer remain an unfulfilled promise. However, recent advances in RNA technology coupled with scientific and clinical breakthroughs have spurred rapid discovery and potent delivery of tumor antigens at speed and scale, transforming cancer vaccines into a tantalizing prospect. Yet, despite being at a pivotal juncture, with several randomized clinical trials maturing in upcoming years, several critical questions remain: which antigens, tumors, platforms, and hosts can trigger potent immunity with clinical impact? Here, we address these questions with a principled framework of cancer vaccination from antigen detection to delivery. With this framework, we outline features of emergent RNA technology that enable rapid, robust, real-time vaccination with somatic mutation-derived neoantigens-an emerging "ideal" antigen class-and highlight latent features that have sparked the belief that RNA could realize the enduring vision for vaccines against cancer.
疫苗是改善健康最具影响力的药物。尽管对病原体有很强的作用，但癌症疫苗仍然是一个未实现的承诺。然而，最近 RNA 技术的进步以及科学和临床突破的结合，促使肿瘤抗原的快速发现和有效传递，使癌症疫苗成为一个诱人的前景。然而，尽管正处于关键的转折点，有几个随机临床试验将在未来几年成熟，仍然存在几个关键问题：哪些抗原、肿瘤、平台和宿主可以引发具有临床影响的有效免疫？在这里，我们用癌症疫苗接种的原则框架来解决这些问题，从抗原检测到传递。有了这个框架，我们概述了新兴的 RNA 技术的特点，这些特点使基于体细胞突变衍生的新抗原的快速、强大、实时疫苗接种成为可能，这是一个新兴的“理想”抗原类，并强调了激发人们相信 RNA 可以实现针对癌症疫苗的持久愿景的潜在特征。
