Application of BCG-CWS as a Systemic Adjuvant by Using Nanoparticulation Technology

Abstract

The intravesical instillation of live Bacillus Calmette-Guerin (BCG) for treating bladder cancer is a powerful cancer immunotherapy. The BCG cell wall skeleton (BCG-CWS) is the main component of the adjuvant, leading to the induction of antitumor immunity. However, the use of live BCG and BCG-CWS is currently limited to local administration because of the infectiousness of live BCG and the insolubility of BCG-CWS. We previously developed a water-dispersible nanoparticle (NP) formulation of BCG-CWS (CWS-NP), which could be used to apply BCG components for use as a systemically injected adjuvant for the treatment of cancers other than bladder cancer. In the present study, we examined the possible use of CWS-NP for cancer immunotherapy, when intravenously administered. The CWS-NP was a highly uniform dispersion and showed no aggregation in serum. The intravenously injected CWS-NP accumulated in the spleen and was efficiently taken up by dendritic cells, leading to their maturation. The coadministration of CWS-NP and ovalbumin (OVA) loaded NP resulted in the generation of OVA-specific cytotoxic T cells and inhibited the growth of E.G7-OVA tumors. These results represent the first findings related to the use of systemically injected CWS-NP as an adjuvant for cancer immunotherapy.

Conducting Polymeric Nanocomposites with a Three-Dimensional Co-flow Microfluidics Platform

“…Nanoparticulation can be implemented through many platforms/techniques [12]. The standard protocol is batch processes [13], which usually has several benefits: very efficient fabrication of a large volume of nanomaterial and conceptually easy in that injection can be performed by one-pot pouring of the organic phase into the aqueous solution.…”

Mycobacteria-Based Vaccines as Immunotherapy for Non-urological Cancers

“…Effect of LM from BCG seemed to be due to both recruitment of DCs that trigger superoxide production by eosinophils and memory Th2 cells [ 161 ]. In another study, maturation of DCs, specific cytolytic T cell activity, and antitumor effect in an ovalbumin (OVA)-expressing EL4 tumor model were seen combining Tokyo BCG strain-CWS formulated in nanoparticles with OVA-loaded nanoparticles [ 162 ].…”

Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine

“…6 A). The intravenous administration of CWS-LNP enhanced the induction of OVA-specific CTL and the growth suppression of E.G7-OVA tumor [ 124 ]. On the other hand, a biochemical analysis in blood after the intravenous administration of CWS-LNP and an evaluation of weight change during the immunization of CWS-LNP suggest that the CWS-LNP caused no side effects.…”

“…However, the CWS-LNP effectively functions as a systemic cancer adjuvant, because it is non-infectious and can be dispersed in water. Reprinted with permission from [ 124 ]. Copyright 2018 American Chemical Society.…”