Mannupulating inate immunity for new vaccine against cancer(Fostering Joint International Research)

• Project/Area Number: 15KK0310
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIDA Tatsuhiro 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (50325271)
• Project Period (FY): 2016 – 2019
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
• Keywords: リポソーム / PEG / TI抗原 / ワクチン

Outline of Final Research Achievements

In this study, we showed a novel antigen (Ab) delivery platform for cancer vaccines that delivers an encapsulated Ag to splenic marginal zone B cells via the aid of a PEGylated liposome (PEG-Lip) system. In mice, preimmunization with empty PEG-Lips triggered the efficient delivery of a subsequent dose of Ag-containing PEG-Lips, injected 3 day later, to the spleen. This immunization induced a cytotoxic T cells (CTL) response against OVA-expressing murine thymoma (EG7-OVA) cells and resulted in in vivo growth inhibition of subsequently inoculated EG7-OVA cells. However, this immunization required repeated immunizations to achieve their antitumor effect. Therefore, to improve their antitumor effect, an adjuvant, aGC, was incorporated into the OVA-PEG-Lips (aGC/OVA-PEG-Lips). As expected, a single immunization treatment efficiently triggered a potent CTL induction, resulting in a rejection of the development and a suppression of the growth of tumors that had already developed s.c.

Academic Significance and Societal Importance of the Research Achievements

本課題の遂行により、静脈投与型の新たなワクチンの開発に繋がる新規な免疫方法が見出された。本免疫方法は脾臓を標的免疫組織としていることから、独自性が高く、皮下投与が主流のこれまでのワクチンとは異なる免疫反応が期待できるため、有用なワクチンの開発に繋がることが期待される。また、本課題の進捗に伴い、新たに課題も見出され、新たな枠組みでの国際共同研究が開始された。学部間交流や大学院生や研究生の交換にもつながっており、意義は大きい。

Research Products

• [Int'l Joint Research] セメルヴァス大学ナノ医薬品研究センター(ハンガリー) (2018)
• [Int'l Joint Research] ブリティッシュコロンビア大学薬学部(カナダ) (2017)
• [Journal Article] Involvement of complement activation in the pulmonary vasoactivity of polystyrene nanoparticles in pigs: Unique surface properties underlying alternative pathway activation and instant opsonization. (2018)
  • Author(s): Meszaros, T., Kozma, G., Shimizu, T., Miyahara, K., Turjeman, K., Ishida, T., Barenholz, Y., Urbanics, R., Szebeni, J.
  • Journal Title: Int. J. Nanomed. Volume: 13 Pages: 6345-6357
  • DOI: 10.2147/ijn.s161369
  • NAID: 120006956857
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Anti-polyethylene-glycol Antibody Response to PEGylated Nanoparticles. (2018)
  • Author(s): Ishida, T.
  • Organizer: CLINAM summit 2018
  • Int'l Joint Research / Invited