2025-12-10 医薬基盤・健康・栄養研究所
<関連情報>
- https://www.nibn.go.jp/pr/press/20251210.html
- https://www.nibn.go.jp/pr/press/documents/20251210.pdf
- https://insight.jci.org/articles/view/196809
非ヒト霊長類モデルにおける経口TLR7作動薬SA-5の前臨床評価 Preclinical assessment of oral TLR7 agonist SA-5 in a non-human primate model
Shokichi Takahama, Takahiro Tomiyama, Sachiyo Yoshio, Yuta Nagatsuka, Hirotomo Murakami, Takuto Nogimori, Mami Kochi, Shoko Ochiai, Hidenori Kimura, Akihisa Fukushima, Tatsuya Kanto, and Takuya Yamamoto
JCI Insight Published: November 11, 2025
DOI:https://doi.org/10.1172/jci.insight.196809
Abstract
Toll-like receptor 7 (TLR7) agonists are promising immunostimulatory agents for the treatment of chronic infections and cancer. However, their systemic toxicity remains a challenge. In this study, SA-5, a novel liver-targeted, orally available TLR7 agonist, was evaluated for pharmacokinetics, safety, and efficacy in young and aged macaques across 1–10 mg/kg repeated doses. Safety was evaluated through hematologic, biochemical, and flow cytometric profiling, while efficacy was assessed via IFN-α production, gene expression of interferon-stimulated genes, and plasmacytoid dendritic cell activation. A principal component analysis (PCA)-based composite scoring system was used to integrate multimodal parameters. SA-5 induced dose-dependent type I IFN with limited systemic inflammation, with 3 mg/kg showing optimal balance. SA-5 had comparable immunostimulatory activity to GS-9620 but with reduced adverse biomarker shifts. In aged macaques, efficacy was maintained with modestly increased safety responses. These findings support SA-5 as a safer next-generation TLR7 agonist effective across age groups, highlighting integrated biomarker profiling in preclinical immunomodulatory drug development.
