Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
Cancer Treat Rev. 2022 Sep;109:102429. doi: 10.1016/j.ctrv.2022.102429. Epub 2022 Jun 22.
Therapeutic vaccines are currently at the forefront of medical innovation. Various endeavors have been made to develop more consolidated approaches to producing nucleic acid-based vaccines, both DNA and mRNA vaccines. These innovations have continued to propel therapeutic platforms forward, especially for mRNA vaccines, after the successes that drove emergency FDA approval of two mRNA vaccines against SARS-CoV-2. These vaccines use modified mRNAs and lipid nanoparticles to improve stability, antigen translation, and delivery by evading innate immune activation. Simple alterations of mRNA structure- such as non-replicating, modified, or self-amplifying mRNAs- can provide flexibility for future vaccine development. For protein vaccines, the use of long synthetic peptides of tumor antigens instead of short peptides has further enhanced antigen delivery success and peptide stability. Efforts to identify and target neoantigens instead of antigens shared between tumor cells and normal cells have also improved protein-based vaccines. Other approaches use inactivated patient-derived tumor cells to elicit immune responses, or purified tumor antigens are given to patient-derived dendritic cells that are activated in vitro prior to reinjection. This review will discuss recent developments in therapeutic cancer vaccines such as, mode of action and engineering new types of anticancer vaccines, in order to summarize the latest preclinical and clinical data for further discussion of ongoing clinical endeavors in the field.
治疗性疫苗目前处于医学创新的前沿。人们一直在努力开发更有效的方法来生产基于核酸的疫苗,包括 DNA 疫苗和 mRNA 疫苗。这些创新继续推动治疗平台向前发展,特别是对于 mRNA 疫苗,此前推动了两种针对 SARS-CoV-2 的 mRNA 疫苗获得紧急 FDA 批准的成功。这些疫苗使用修饰后的 mRNA 和脂质纳米粒来提高稳定性、抗原翻译效率,并通过逃避先天免疫激活来实现递呈。简单改变 mRNA 结构,如非复制、修饰或自我扩增的 mRNA,可以为未来疫苗的开发提供灵活性。对于蛋白质疫苗,使用肿瘤抗原的长合成肽而不是短肽,进一步提高了抗原递呈的成功率和肽的稳定性。努力识别和靶向新抗原而不是肿瘤细胞和正常细胞之间共享的抗原,也提高了基于蛋白质的疫苗的效果。其他方法使用失活的患者来源的肿瘤细胞来引发免疫反应,或者将纯化的肿瘤抗原给予体外激活的患者来源的树突状细胞,然后再进行回输。本文将讨论治疗性癌症疫苗的最新进展,如作用模式和新型抗癌疫苗的工程设计,以总结最新的临床前和临床数据,进一步讨论该领域正在进行的临床研究。