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mRNA 癌症疫苗:构建与增强策略。

mRNA Cancer Vaccines: Construction and Boosting Strategies.

机构信息

School of Advanced Materials and Nanotechnology, Xidian University, Xi'an 710126 China.

Ministry of Education, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Xi'an, Shaanxi 710126, China.

出版信息

ACS Nano. 2023 Oct 24;17(20):19550-19580. doi: 10.1021/acsnano.3c05635. Epub 2023 Oct 11.

Abstract

In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for the prevention of COVID-19, which has pushed this field to be more closely studied and motivated researchers to delve deeper into mRNA therapeutics. To date, the research on mRNA cancer vaccines has been developed rapidly, and substantial hopeful therapeutic results have been achieved against various solid tumors in clinical trials. In this review, we first introduce three main components of mRNA cancer vaccines, including mRNA antigens, adjuvants, and delivery vectors. Engineering these components can optimize the therapeutic effects of mRNA cancer vaccines. For instance, appropriate modification of mRNA structure can alleviate the poor stability and innate immunogenicity of mRNA, and the use of mRNA delivery vectors can address the issues of low delivery efficiency . Second, we emphatically discuss some strategies to further improve the efficacy of mRNA cancer vaccines, namely modulating the immunosuppressive tumor environment, optimizing administration routes, achieving targeting delivery to intended tissues or organs, and employing combination therapy. These strategies can strengthen the tumor inhibitory ability of mRNA cancer vaccines and increase the possibility of tumor elimination. Finally, we point out some challenges in the clinical practice of mRNA cancer vaccines and offer our perspectives on future developments in this rapidly evolving field. It is anticipated that mRNA cancer vaccines will be rapidly developed for clinical cancer therapy in the near future.

摘要

2020 年末,美国食品和药物管理局(FDA)批准了一种基于脂质的 mRNA 疫苗,用于预防 COVID-19,这促使该领域的研究更加密切,并促使研究人员深入研究 mRNA 疗法。迄今为止,mRNA 癌症疫苗的研究发展迅速,在临床试验中针对各种实体瘤取得了实质性的有希望的治疗结果。在这篇综述中,我们首先介绍了 mRNA 癌症疫苗的三个主要组成部分,包括 mRNA 抗原、佐剂和递送载体。对这些成分进行工程改造可以优化 mRNA 癌症疫苗的治疗效果。例如,适当修饰 mRNA 结构可以缓解 mRNA 的稳定性差和固有免疫原性低的问题,而使用 mRNA 递送载体可以解决递送效率低的问题。其次,我们着重讨论了一些进一步提高 mRNA 癌症疫苗疗效的策略,即调节免疫抑制性肿瘤微环境、优化给药途径、实现靶向递送到预期的组织或器官,以及采用联合治疗。这些策略可以增强 mRNA 癌症疫苗的肿瘤抑制能力,增加肿瘤消除的可能性。最后,我们指出了 mRNA 癌症疫苗在临床实践中面临的一些挑战,并对这一快速发展领域的未来发展提出了我们的看法。预计在不久的将来,mRNA 癌症疫苗将迅速发展用于临床癌症治疗。

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