mRNA vaccine for cancer immunotherapy.

文献信息

DOI	10.1186/s12943-021-01335-5
PMID	33632261
期刊	Molecular cancer
影响因子	33.9
JCR 分区	Q1
发表年份	2021
被引次数	419
关键词	癌症免疫疗法, 癌症疫苗, 可离子化脂质, 脂质纳米颗粒（LNPs）, 个性化疫苗
文献类型	Journal Article, Research Support, N.I.H., Extramural, Review
ISSN	1476-4598
页码	41
期号	20(1)
作者	Lei Miao, Yu Zhang, Leaf Huang

一句话小结

mRNA疫苗作为癌症免疫治疗的新兴平台，能够有效激活抗原呈递细胞并刺激免疫反应，但其应用受到稳定性和递送效率等问题的挑战。通过对mRNA结构的优化及与其他免疫疗法的联合使用，研究显示其在提高抗肿瘤免疫和治疗效果方面具有潜力，为未来的癌症治疗提供了新的方向。

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癌症免疫疗法 · 癌症疫苗 · 可离子化脂质 · 脂质纳米颗粒（LNPs） · 个性化疫苗

摘要

mRNA疫苗已成为癌症免疫治疗的一个有前景的平台。在疫苗接种过程中，裸露或载体加载的mRNA疫苗能够有效地在抗原呈递细胞（APCs）中表达肿瘤抗原，促进APC的激活以及先天/适应性免疫的刺激。由于其高效性、安全性、快速开发潜力以及成本效益，mRNA癌症疫苗在其他传统疫苗平台之前取得了领先。然而，mRNA疫苗的应用受到不稳定性、先天免疫原性和体内递送效率低下的限制。为了解决这些问题，研究人员对mRNA结构进行了适当的修改（如密码子优化、核苷酸修饰、自扩增mRNA等）以及配方方法（如脂质纳米颗粒（LNPs）、聚合物、肽等）进行了探索。调节给药途径和与其他免疫治疗剂（如检查点抑制剂）共同递送多种mRNA疫苗进一步增强了宿主的抗肿瘤免疫，提高了肿瘤细胞清除的可能性。随着美国食品药品监督管理局（FDA）批准LNP加载的mRNA疫苗用于预防COVID-19，以及在多项针对多种侵袭性实体瘤的临床试验中取得的有希望的mRNA癌症疫苗治疗结果，我们展望mRNA疫苗在癌症免疫治疗领域的快速进展。本文综述了mRNA癌症疫苗的最新进展、现存挑战及未来在癌症免疫治疗中应用mRNA疫苗的考虑。

英文摘要

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

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主要研究问题

核心洞察

研究背景和目的

mRNA疫苗在癌症免疫治疗中展现出巨大的潜力。相较于传统疫苗，mRNA疫苗具有高效、快速开发和安全性高等优势，但其应用受到稳定性、内源性免疫原性和体内递送效率的限制。本研究旨在综述mRNA癌症疫苗的最新进展、面临的挑战以及未来的发展方向。

主要方法/材料/实验设计

本研究采用文献综述的方式，重点分析了mRNA疫苗的结构修饰、递送系统以及与其他免疫治疗的联合应用。以下是研究的技术路线图：

关键结果和发现

结构修饰：通过对mRNA的密码子和核苷酸进行优化，提高了其稳定性和翻译效率。自扩增mRNA(SAM)显示出更长的免疫反应持续时间。
递送系统：脂质纳米颗粒(LNP)被广泛应用于mRNA递送，能够有效保护mRNA并提高其细胞摄取效率。其他递送系统如聚合物和肽也在研究中展现出良好的前景。
联合治疗：将mRNA疫苗与检查点抑制剂和细胞因子联合使用，显著增强了抗肿瘤免疫反应，改善了治疗效果。

主要结论/意义/创新性

mRNA疫苗作为癌症免疫治疗的一种新型策略，具备了同时编码多种抗原的能力，并能够激活细胞免疫和体液免疫反应。与传统癌症疫苗相比，mRNA疫苗在制造速度和个性化治疗方面具有显著优势。随着技术的不断进步，mRNA疫苗在癌症治疗中的应用前景广阔。

研究局限性和未来方向

尽管mRNA疫苗在临床试验中展现出良好的安全性和有效性，但仍面临抗原选择困难和抑制性肿瘤微环境等挑战。未来的研究应重点关注：

提高免疫原性：通过更精确的抗原设计和个性化疫苗开发来克服免疫逃逸。
优化递送系统：研发更安全有效的递送载体，以提高mRNA的体内稳定性和递送效率。
临床转化：加强对mRNA疫苗的临床试验，以验证其在不同癌症类型中的疗效。

通过解决上述挑战，mRNA疫苗有望在癌症免疫治疗中发挥更大的作用。

参考文献

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... (409 更多篇文献)

mRNA vaccine for cancer immunotherapy. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​