Neutrophil-Mediated Tumor-Targeting Delivery System of Oncolytic Bacteria Combined with ICB for Melanoma Lung...

Area of Science:

• Oncolytic virotherapy and immunotherapy
• Bacterial cancer therapy
• Drug delivery systems

Background:

• Oncolytic bacteria show promise for cancer treatment but require improved tumor targeting and safety.
• Attenuated Salmonella typhimurium (VNP20009) is a clinically evaluated candidate for oncolytic therapy.
• Balancing therapeutic efficacy and safety is crucial for oncolytic bacteria development.

Purpose of the Study:

• To develop a neutrophil-based delivery system for controlled release of oncolytic bacteria (VNP20009).
• To enhance the anti-tumor efficacy of oncolytic bacteria by incorporating a PD1 nanobody (NE(PD1nb)).
• To investigate the immune-modulating effects of the NE(PD1nb) system.

Main Methods:

• Loading VNP20009 into neutrophils to create a targeted delivery system.
• Constructing a novel system (NE(PD1nb)) by applying a PD1 nanobody to the neutrophil-VNP20009 complex.
• Evaluating the therapeutic efficacy in a melanoma lung metastasis model.
• Assessing the impact on immune cells, including dendritic cells, macrophages, CD4+, and CD8+ T-cells.

Main Results:

• The neutrophil-loaded VNP20009 system significantly improved tumor targeting and therapeutic efficacy.
• NE(PD1nb) demonstrated enhanced synergistic therapeutic effects compared to VNP20009 alone.
• NE(PD1nb) promoted dendritic cell differentiation, M1-like macrophage polarization, and activation of CD4+ and CD8+ T-cells via antigen presentation.

Conclusions:

• Neutrophil-mediated delivery of oncolytic bacteria enhances tumor colonization and therapeutic outcomes.
• The addition of a PD1 nanobody to the delivery system amplifies anti-tumor immunity and efficacy.
• This engineered system offers a promising strategy for synergistic cancer therapy by combining oncolytic bacteria and immunotherapy.