Development of a novel hyperthermic immunotherapy by selective delivery of nano-DDS and therapeutic molecules for pancreas cancer treatment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03387
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Chiba University
• Principal Investigator: Hiroto Hatakeyama 千葉大学, 大学院薬学研究院, 准教授 (70504786)
• Co-Investigator(Kenkyū-buntansha): 新留 琢郎 熊本大学, 大学院先端科学研究部(工), 教授 (20264210) ; 佐野 誠 (SanoMakoto) 日本大学, 医学部, 准教授 (70339323)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腹腔内投与 / 免疫チェックポイント阻害剤 / 腹膜播種 / 脂質ナノ粒子 / 温熱療法

Outline of Final Research Achievements

Therapeutic outcomes of immune checkpoint inhibitors (ICIs) for pancreatic cancer and peritoneal dissemination are not efficient due to poor drug delivery. We found that intraperitoneal (ip) administration of ICIs and lipid nanoparticles (LNPs), which is different from clinically utilized intravenous (iv) injection, increased the delivered amount of ICIs and LNPs by 10-fild compared to iv injection. ip injected ICIs and LNPs directly penetrated to ip tumors, which resulted in superior therapeutic efficacy to iv injection. These findings provide the basis for the development of a novel thermo-immunotherapy for pancreatic cancer and peritoneal dissemination by ICIs and hyperthermia with inhibition of a thermoresistant mechanism by delivering nucleic acids molecules with LNPs using ip route.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤(ICI)は臨床で静脈内(iv)投与されるが、腹腔内腫瘍への送達効率は悪く十分な治療効果は得られていない。本研究を通じて、腹腔内(ip)投与はICIの腹腔内腫瘍への送達のメカニズムを評価し腹膜播種治療に有用な投与経路であることを明らかとした。本知見は100ナノメートルの脂質ナノ粒子(LNP)にも適応され、LNPを用いた核酸医薬による腹膜播種治療の可能性を拓くものである。本研究で得られた知見は、今後膵癌をはじめ腹膜播種を伴う予後が極めて悪い難治性疾患治療におけるip投与経路の臨床研究への基盤となる。