Study of nanoparticles-incorporating immune modulating oligodeoxynucleotide for the treatment of lung diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: SATO Takashi 横浜市立大学, 医学部, 講師 (70510436)
• Co-Investigator(Kenkyū-buntansha): 下里 剛士 信州大学, 学術研究院農学系, 准教授 (00467200)
• Research Collaborator: Klinman Dennis
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ナノメディシン / ドラッグデリバリー / 肺癌 / 肺気腫 / 動物モデル

Outline of Final Research Achievements

We have developed inhalable particles-incorporating synthetic oligodeoxynucleotides (ODN) for treating lung diseases. To evaluate the efficacy against lung cancer, we developed a lethal model mimicking primary lung cancer by intratracheal instillation of Lewis lung carcinoma (LLC) cells in C57BL/6 mice, resulting in peribronchial tumor formation with an approximately 22-day median survival. Long-term survivors after treatment with intratracheal administration of particles-incorporating Th1 stimulating ODN were further re-challenged with LLC cells. Although mild-to-moderate alopecia was seen in about 30% of mice that survived for 1 year after previous particle-incorporating ODN treatment, other markers/symptoms of organ damage were not apparent. Histological analysis showed down-regulation of CD3(+)Foxp3(+) and PD-1(+) cells in lung residual tumors in re-challenged mice, leading 100% survival at 1 year by maintaining long-term tumor immunity, and thus preventing cancer recurrence.

Free Research Field

呼吸器病学