title: Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model.
abstract: 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. Tumor growth was significantly inhibited in mice that had been inoculated with mouse bladder cancer (MBT-2) cells containing internalized BCG-CWS. On the other hand, the internalization of BCG-CWS by DCs had only a minor effect on inducing an antitumor effect against MBT-2 tumors. This was clarified for the first time by using the CWS-NP. This finding provides insights into our understanding of the role of bladder cancer cells and DCs in BCG therapy against bladder cancer.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukiage
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Japan BCG Central Laboratory, Kiyose, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.affiliation: Department of Urology, Faculty of Medicine, Tsukuba University, Tsukuba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Faculty of Medicine, Tsukuba University, Tsukuba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.affiliation: The University of Tokyo, Research Center for Advanced Science and Technology, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001500:BCG Vaccine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017358:Cell Wall Skeleton / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects; D004655:Emulsions; D005260:Female; D007958:Leukocyte Count; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008809:Mice, Inbred C3H; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D017358:Cell Wall Skeleton; D004655:Emulsions; D008055:Lipids
keywords: BCG-CWS; Bladder cancer; Cancer immunotherapy; Delivery system; Nanoparticle