SCI
28 June 2024
RNA vaccines for cancer: Principles to practice
(Cancer Cell, IF: 48.8)
Pablo Guasp, Charlotte Reiche, Zachary Sethna, and Vinod P. Balachandran
CORRESPONDENCE TO: balachav@mskcc.org
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.
疫苗是改善健康最有效的药物。尽管癌症疫苗对病原体有很强的抵抗力,但它仍是一个未实现的承诺。然而,RNA技术的最新进展加上科学和临床的突破,刺激了肿瘤抗原的快速发现和快速大规模的有效递送,将癌症疫苗转变为美好的前景。然而,尽管正处于一个关键时刻,随着数项随机临床试验在未来几年的成熟,一些关键问题仍然存在:哪些抗原、肿瘤、平台和宿主可以诱发具有临床影响的强大免疫力?在这里,我们用接种癌症疫苗从抗原检测到递送的原则框架来解决这些问题。在这个框架下,我们概述了新兴RNA技术的特点,这些技术能够快速、稳健、实时地接种体细胞突变衍生的新抗原(一种新兴的“处理”抗原类别),并强调了潜在的特征,这些特征激发了实现癌症RNA疫苗的持久愿景。