探索潜力:肿瘤学中的mRNA疗法。

Unraveling the potential: mRNA therapeutics in oncology.

作者信息

Gawalski Karol, Przybyszewska Weronika, Hunia Jaromir, Gawalska Alicja, Rymarz Aleksandra

机构信息

Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland.

Doctoral School, Medical University of Warsaw, Warsaw, Poland.

出版信息

Front Oncol. 2025 Aug 13;15:1643444. doi: 10.3389/fonc.2025.1643444. eCollection 2025.

Abstract

Messenger ribonucleic acid (mRNA) technology is a promising platform for cancer immunotherapy. Unlike traditional vaccines that prevent infectious diseases, mRNA's role in oncology is to stimulate or enhance the immune response against tumor antigens. This review provides an overview of mRNA's historical development, from its discovery in 1961 to recent clinical trials and Nobel Prize-winning breakthroughs. Therapeutic mRNA flexibility allows the alteration of diverse tumor antigens. Key targets include tumor-associated antigens, which are present on both tumor cells and some healthy cells, as well as tumor-specific antigens unique to cancer cells, such as antiviral antigens and neoantigens arising from tumor mutations. Various approaches to protect mRNA from degradation, including protamine-complexed mRNA, lipoplexes, and lipid nanoparticles, as well as several administration routes, are currently being tested in clinical trials. They are focused on malignancies like melanoma, non-small cell lung cancer, prostate cancer, or pancreatic ductal adenocarcinoma, one of the most challenging cancers. While many trials are in early phases, some have advanced to phase 3 and have shown promising results in both safety and efficacy. However, due to the complexity and heterogeneity of tumors, even among patients presenting the same subgroup of neoplasm, fully universal mRNA-based cancer vaccine seems to be elusive. Personalized mRNA cancer vaccines targeting neoantigens unique to an individual's tumor have gained traction as a feasible and promising solution. Technological advances in bioinformatics, AI, and machine learning now allow for more accurate identification of immunogenic neoepitopes. The combination this type of therapy with other treatment such as immune checkpoint inhibitors may become one of new solutions in oncology.

摘要

信使核糖核酸(mRNA)技术是癌症免疫治疗中一个很有前景的平台。与预防传染病的传统疫苗不同,mRNA在肿瘤学中的作用是刺激或增强针对肿瘤抗原的免疫反应。本综述概述了mRNA的历史发展,从1961年被发现到近期的临床试验以及获得诺贝尔奖的突破。治疗性mRNA的灵活性允许改变多种肿瘤抗原。关键靶点包括肿瘤相关抗原,其存在于肿瘤细胞和一些健康细胞上,以及癌细胞特有的肿瘤特异性抗原,如抗病毒抗原和由肿瘤突变产生的新抗原。目前正在临床试验中测试多种保护mRNA不被降解的方法,包括鱼精蛋白复合mRNA、脂质体和脂质纳米颗粒,以及几种给药途径。这些试验聚焦于黑色素瘤、非小细胞肺癌、前列腺癌或胰腺导管腺癌等恶性肿瘤,胰腺导管腺癌是最具挑战性的癌症之一。虽然许多试验处于早期阶段,但有些已进入3期,并在安全性和有效性方面都显示出了有希望的结果。然而,由于肿瘤的复杂性和异质性,即使在呈现相同肿瘤亚组的患者中,完全通用的基于mRNA的癌症疫苗似乎也难以实现。针对个体肿瘤特有的新抗原的个性化mRNA癌症疫苗作为一种可行且有前景的解决方案已受到关注。生物信息学、人工智能和机器学习方面的技术进步现在能够更准确地识别免疫原性新表位。这种类型的疗法与免疫检查点抑制剂等其他治疗方法的联合应用可能会成为肿瘤学中的新解决方案之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc81/12381778/bad817905749/fonc-15-1643444-g001.jpg

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