2024-02-14 コロンビア大学
◆UCアーバイン校のKe Cheng教授らの研究チームが、1月11日にNature Nanotechnologyに掲載された論文で、ナノバブルであるエクソソームを使用して、吸入治療法を介してIL-12メッセンジャーRNA(mRNA)を肺に直接送達することができることを示した。これにより、副作用を最小限に抑えながら、腫瘍と闘うことができる。
<関連情報>
- https://www.engineering.columbia.edu/news/study-finds-new-inhalable-therapy-big-step-forward-lung-cancer-research
- https://www.nature.com/articles/s41565-023-01580-3
肺がんの治療と全身性免疫の促進を目的としたIL-12 mRNAの吸入可能な細胞外小胞デリバリー Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity
Mengrui Liu,Shiqi Hu,Na Yan,Kristen D. Popowski & Ke Cheng
Nature Nanotechnology Published:11 January 2024
DOI:https://doi.org/10.1038/s41565-023-01580-3
Abstract
Lung carcinoma is one of the most common cancers and has one of the lowest survival rates in the world. Cytokines such as interleukin-12 (IL-12) have demonstrated considerable potential as robust tumour suppressors. However, their applications are limited due to off-target toxicity. Here we report on a strategy involving the inhalation of IL-12 messenger RNA, encapsulated within extracellular vesicles. Inhalation and preferential uptake by cancer cells results in targeted delivery and fewer systemic side effects. The IL-12 messenger RNA generates interferon-γ production in both innate and adaptive immune-cell populations. This activation consequently incites an intense activation state in the tumour microenvironment and augments its immunogenicity. The increased immune response results in the expansion of tumour cytotoxic immune effector cells, the formation of immune memory, improved antigen presentation and tumour-specific T cell priming. The strategy is demonstrated against primary neoplastic lesions and provides profound protection against subsequent tumour rechallenge. This shows the potential for locally delivered cytokine-based immunotherapies to address orthotopic and metastatic lung tumours.
