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用于癌症免疫治疗的信使核糖核酸疗法的修饰与递送进展。

Progress in modifying and delivering mRNA therapies for cancer immunotherapy.

作者信息

Goel Karan, Chawla Isha, Dhanawat Meenakshi, Chaubey Pramila

机构信息

M.M College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, India.

Amity Institute of Pharmacy, Amity University Haryana, Amity Education Valley, Panchgaon, Manesar, Gurugram, Haryana, India.

出版信息

Adv Immunol. 2025;165:89-115. doi: 10.1016/bs.ai.2024.10.004. Epub 2024 Dec 2.

Abstract

Advancements in mRNA-based therapeutics have greatly enhanced cancer immunotherapy by using the immune system to specifically target and eradicate cancer cells. There has been notable advancement in tailoring and administering mRNA to treat cancer. Codon optimization, chemical alterations, and sequence manipulation are complex design methodologies employed in the production of mRNA vaccines and treatments. The goal is to improve the ability of the chemicals to stimulate an immune response, increase their ability to be translated into practical applications, and boost their stability. Lipid nanoparticles (LNPs) are currently the most efficient means of delivering mRNA because they can withstand degradation, enhance cellular uptake, and facilitate endosomal escape. Scientists are currently investigating the possibility of using alternate methods of delivering substances, including as exosomes, lipoplexes, and polymeric nanoparticles, to enhance the ability to target specific tissues and minimize unwanted negative consequences. In addition, recent clinical trials and preclinical investigations have demonstrated encouraging findings in terms of the advancement of strong anti-tumor immune responses, long-lasting tumor shrinkage, and enhanced patient outcomes. The remaining challenges involve optimizing the equilibrium between tolerance and immunological activation, addressing systemic toxicity, and expanding manufacturing techniques. The upcoming study seeks to improve the design and dissemination of mRNA, include it in combination drugs, and investigate its therapeutic uses outside cancer. The advancement in cancer treatment represents a change in the current approach, highlighting the significant impact of mRNA technology in revolutionizing immunotherapy and enabling tailored cancer treatments.

摘要

基于信使核糖核酸(mRNA)的治疗方法取得的进展,通过利用免疫系统特异性地靶向和根除癌细胞,极大地增强了癌症免疫疗法。在定制和施用mRNA以治疗癌症方面取得了显著进展。密码子优化、化学修饰和序列操纵是用于生产mRNA疫苗和治疗方法的复杂设计方法。目标是提高化学物质刺激免疫反应的能力,增强其转化为实际应用的能力,并提高其稳定性。脂质纳米颗粒(LNPs)目前是递送mRNA最有效的手段,因为它们能够抵抗降解、增强细胞摄取并促进内体逃逸。科学家们目前正在研究使用包括外泌体、脂质复合物和聚合物纳米颗粒在内的替代物质递送方法的可能性,以提高靶向特定组织的能力并将不良负面后果降至最低。此外,最近的临床试验和临床前研究在增强抗肿瘤免疫反应、持久的肿瘤缩小以及改善患者预后方面取得了令人鼓舞的结果。剩下的挑战包括优化耐受性和免疫激活之间的平衡、解决全身毒性以及扩大制造技术。即将开展的研究旨在改进mRNA的设计和传播,将其纳入联合药物,并研究其在癌症以外的治疗用途。癌症治疗方面的进展代表了当前方法的一种转变,突出了mRNA技术在革新免疫疗法和实现个性化癌症治疗方面的重大影响。

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