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

Area of Science:

• Immunology
• Nanotechnology
• Oncology

Background:

• Bacillus Calmette-Guerin (BCG) and its cell wall skeleton (BCG-CWS) are established cancer immunotherapies, primarily for bladder cancer.
• Current limitations include the infectiousness of live BCG and the insolubility of BCG-CWS, restricting them to local administration.
• A novel water-dispersible nanoparticle formulation of BCG-CWS (CWS-NP) was previously developed for potential systemic use.

Purpose of the Study:

• To investigate the efficacy of systemically administered CWS-NP as an adjuvant for cancer immunotherapy.
• To evaluate the biodistribution, immune cell interaction, and anti-tumor effects of intravenously injected CWS-NP.

Main Methods:

• Development of a stable, water-dispersible CWS-NP formulation.
• Intravenous administration of CWS-NP in preclinical models.
• Assessment of CWS-NP aggregation in serum, spleen accumulation, dendritic cell uptake and maturation, and T cell responses.
• Evaluation of tumor growth inhibition when CWS-NP was co-administered with antigen-loaded nanoparticles.

Main Results:

• CWS-NP demonstrated uniform dispersion and stability in serum without aggregation.
• Intravenously injected CWS-NP localized to the spleen and was effectively internalized by dendritic cells, promoting their maturation.
• Coadministration of CWS-NP with ovalbumin (OVA)-loaded nanoparticles induced OVA-specific cytotoxic T cells.
• Significant inhibition of E.G7-OVA tumor growth was observed with CWS-NP co-treatment.

Conclusions:

• Systemic administration of CWS-NP is a viable strategy for cancer immunotherapy.
• CWS-NP effectively enhances anti-tumor immunity by activating dendritic cells and promoting cytotoxic T cell responses.
• These findings open new avenues for developing systemic nanoparticle-based BCG adjuvants for various cancers.