利用mRNA脂质纳米颗粒靶向癌症：关键考虑因素和未来展望

SCI

29 August 2023

Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects

（Nature reviews. Clinical oncology；IF：78.8）

Kon, E., Ad-El, N., Hazan-Halevy, I. et al. Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects. Nat Rev Clin Oncol (2023). https://doi.org/10.1038/s41571-023-00811-9

Correspondence to:Edo Kon, Nitay Ad-El. Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.e-mail: peer@tauex.tau.ac.il

Abstract 摘要

Harnessing mRNA–lipid nanoparticles (LNPs) to treat patients with cancer has been an ongoing research area that started before these versatile were successfully used as COVID-19 vaccines. Currently, efforts are underway to harness this platform for oncology therapeutics, mainly focusing on cancer vaccines targeting multiple neoantigens or direct intratumoural injections of mRNA–LNPs encoding pro-infammatory cytokines. In this Review, we describe the opportunities of using mRNA–LNPs in oncology applications and discuss the challenges for successfully translating the fndings of preclinical studies of these nanoparticles into the clinic. We critically appraise the potential of various mRNA–LNP targeting and delivery strategies, considering physiological, technological and manufacturing challenges. We explore these approaches in the context of the potential clinical applications best suited to each approach and highlight the obstacles that currently need to be addressed to achieve these applications. Finally, we provide insights from preclinical and clinical studies that are leading to this powerful platform being considered the next frontier in oncology treatment.

利用mRNA-脂质纳米颗粒（LNPs）来治疗癌症患者一直是一个火热进行中的研究领域，该领域的发展早于这些多功能纳米颗粒成功应用于COVID-19疫苗。目前，正在努力利用这个平台用于肿瘤治疗，主要集中在开发针对多种新抗原的癌症疫苗，或直接在肿瘤内注射编码促炎细胞因子的mRNA-LNP。在这篇综述中，我们描述了在肿瘤学应用中使用mRNA-LNPs的可能，并讨论了将这些纳米颗粒的临床前研究发现成功转化为临床实践的挑战。我们考虑到生理、技术和制造方面的挑战，批判地评估了各种mRNA-LNP靶向和传递策略的潜力。我们在最适合每种方法的潜在临床应用的背景下探索了这些方法，并强调目前实现这些应用需要解决的障碍。最后，我们提供了来自临床前和临床研究的见解，这些研究将此强大平台视为肿瘤治疗的下一个前沿。