Pahwa Rakesh, Sharma Gulshan, Panwar Rohil, Mishra Neeraj
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India.
Professor and Head of Department, Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India.
Adv Immunol. 2025;166:77-101. doi: 10.1016/bs.ai.2024.10.012. Epub 2025 Feb 4.
The emergence of mRNA-based cancer immunotherapy has transformed the avenue of cancer treatment, offering an innovative strategy that leverages the body's immune system to identify and eradicate tumor cells selectively. Effective delivery of mRNA to specific organs and cells is limited by its instability, low cellular uptake efficiency, and degradation during extracellular transport and endosomal escape. Significant advancements in nanoparticle design have driven the rapid progress of mRNA-based immunotherapies. Nanocarriers have emerged as vital delivery systems, providing enhanced stability, resistance to enzymatic degradation, and efficient mRNA delivery to target cells. This chapter investigates the design, synthesis, and functionalization of different types of nanoparticles, including lipid-based, polymeric, and hybrid nanoparticles and also highlights their unique characteristics and mechanisms for mRNA delivery in cancer immunotherapy. This chapter explores cellular uptake mechanisms, strategies for endosomal escape, and the subsequent translation of mRNA into therapeutic proteins that elicit a vigorous anti-tumor immune response. Recent advances in nanoparticle-based mRNA vaccines are also explored, with an emphasis on research findings and clinical trials that reveal both their potential and challenges. The chapter aims to provide a thorough overview of nanoparticle integration in mRNA-based cancer immunotherapy and also offer insights into future developments and emerging trends in the field.
基于mRNA的癌症免疫疗法的出现改变了癌症治疗的途径,提供了一种创新策略,即利用人体免疫系统选择性地识别和根除肿瘤细胞。mRNA向特定器官和细胞的有效递送受到其不稳定性、低细胞摄取效率以及细胞外运输和内体逃逸过程中的降解的限制。纳米颗粒设计的重大进展推动了基于mRNA的免疫疗法的快速发展。纳米载体已成为至关重要的递送系统,具有增强的稳定性、抗酶降解能力以及将mRNA有效递送至靶细胞的能力。本章研究了不同类型纳米颗粒的设计、合成和功能化,包括基于脂质的、聚合物的和混合纳米颗粒,并突出了它们在癌症免疫疗法中进行mRNA递送的独特特性和机制。本章探讨了细胞摄取机制、内体逃逸策略以及随后将mRNA翻译成引发强烈抗肿瘤免疫反应的治疗性蛋白质的过程。还探讨了基于纳米颗粒的mRNA疫苗的最新进展,重点是揭示其潜力和挑战的研究结果和临床试验。本章旨在全面概述纳米颗粒在基于mRNA的癌症免疫疗法中的整合情况,并对该领域的未来发展和新趋势提供见解。