Department of Surgery, Duke University, Durham, NC, USA.
Department of Pathology, Duke University, Durham, NC, USA.
Cancer Gene Ther. 2023 Jun;30(6):794-802. doi: 10.1038/s41417-022-00499-6. Epub 2022 Jul 12.
The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity, making srRNA vectors ideal candidates for anti-tumor vaccination. In this review, we summarize different types of srRNA platforms that have emerged and review evidence for their efficacy in provoking anti-tumor immunity to different antigens. These srRNA platforms encompass the use of naked RNA, DNA-launched replicons, viral replicon particles (VRP), and most recently, synthetic srRNA replicon particles. Across these platforms, studies have demonstrated srRNA vaccine platforms to be potent inducers of anti-tumor immunity, which can be enhanced by homologous vaccine boosting and combining with chemotherapies, radiation, and immune checkpoint inhibition. As such, while this remains an active area of research, the past and present trajectory of srRNA vaccine development suggests immense potential for this platform in producing effective cancer vaccines.
基于 RNA 的 SARS-CoV-2 疫苗的开发和成功激发了人们对利用 RNA 疫苗治疗癌症的新兴趣，特别是在新兴的自我复制 RNA（srRNA）病毒疫苗平台的应用方面。这些疫苗基于不同的单链 RNA 病毒，除了复制基因外，它们还编码针对靶抗原的 RNA，这些复制基因能够在感染后大量扩增 RNA 信息。编码的复制酶基因还能刺激先天免疫，使 srRNA 载体成为抗肿瘤疫苗的理想候选物。在这篇综述中，我们总结了不同类型的 srRNA 平台，并回顾了它们在引发针对不同抗原的抗肿瘤免疫方面的有效性证据。这些 srRNA 平台包括使用裸露的 RNA、DNA 启动的复制子、病毒复制子颗粒（VRP），以及最近的合成 srRNA 复制子颗粒。在这些平台上，研究表明 srRNA 疫苗平台能够有效地诱导抗肿瘤免疫，通过同源疫苗增强和与化疗、放疗和免疫检查点抑制联合使用，可以进一步增强这种免疫。因此，尽管这仍然是一个活跃的研究领域，但 srRNA 疫苗开发的过去和现在轨迹表明，该平台在生产有效癌症疫苗方面具有巨大的潜力。
