Esprit Arthur, de Mey Wout, Bahadur Shahi Rajendra, Thielemans Kris, Franceschini Lorenzo, Breckpot Karine
Laboratory for Molecular and Cellular Therapy (LMCT), Department of Biomedical Sciences, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
Vaccines (Basel). 2020 Dec 18;8(4):776. doi: 10.3390/vaccines8040776.
The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. Neo-antigens are cancer-specific antigens, which develop from somatic mutations in the cancer cell genome that can be highly immunogenic and are not subjected to central tolerance. As the majority of neo-antigens are unique to each patient's cancer, a vaccine technology that is flexible and potent is required to develop personalized neo-antigen vaccines. In vitro transcribed mRNA is such a technology platform and has been evaluated for delivery of neo-antigens to professional antigen-presenting cells both ex vivo and in vivo. In addition, strategies that support the activity of T cells in the tumor microenvironment have been developed. These represent a unique opportunity to ensure durable T cell activity upon vaccination. Here, we comprehensively review recent progress in mRNA-based neo-antigen vaccines, summarizing critical milestones that made it possible to bring the promise of therapeutic cancer vaccines within reach.
近年来，由于癌症研究取得了多项突破，治疗性癌症疫苗引发了极大关注，其中包括成功的免疫检查点阻断治疗可使新抗原特异性T细胞恢复活力，以及成功的过继性细胞疗法针对新抗原。新抗原是癌症特异性抗原，由癌细胞基因组中的体细胞突变产生，具有高度免疫原性且不受中枢耐受的影响。由于大多数新抗原是每个患者癌症所特有的，因此需要一种灵活且有效的疫苗技术来开发个性化新抗原疫苗。体外转录mRNA就是这样一种技术平台，已在体外和体内评估了其将新抗原递送至专业抗原呈递细胞的能力。此外，还开发了支持肿瘤微环境中T细胞活性的策略。这些为确保接种疫苗后T细胞的持久活性提供了独特机会。在此，我们全面综述基于mRNA的新抗原疫苗的最新进展，总结使治疗性癌症疫苗有望成为现实的关键里程碑。
