The effect of intracellular trafficking of BCG-CWS loaded nanoparticles on anti-bladder cancer activity

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560231
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Hokkaido University
• Principal Investigator: NAKAMURA Takashi 北海道大学, 薬学研究科(研究院), 助教 (20604458)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 膀胱がん / BCG / 脂質ナノ粒子 / がん免疫療法

Outline of Final Research Achievements

We previously reported on the development of a water soluble formulation of the cell wall skeleton of BCG (BCG-CWS), a major immune active center of BCG, by encapsulating it into a nanoparticle (CWS-NP). The CWS-NP allowed us to clarify the machinery associated with the BCG mediated anti-bladder tumor effect, especially the roles of bladder cancer cells and dendritic cells (DCs) in the initial step, which remains poorly understood. We show herein that the internalization of BCG-CWS by bladder cancer cells, but not DCs, is indispensable for the induction of an antitumor effect against bladder cancer. Moreover, we investigated the effect of intracellular trafficking of lipid antigen loaded nanoparticles on CD1 antigen presentation. The CD1 antigen presentation is appeared to influence to anti-bladder cancer immune responses. Our study revealed that the accumulation of lipid antigen loaded nanoparticles in endosomes/lysosomes efficiently enhanced CD1 antigen presentation.

Free Research Field

薬物送達システム　がん免疫