Salmonella vector creates de novo parvovirus that reduces solid tumors and forms antitumor immune memory

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Oncolytic viruses (OVs) show promise for cancer therapy but face challenges with systemic clearance and tumor targeting.
• Effective delivery of OVs to internal solid tumors remains a significant hurdle in clinical applications.

Purpose of the Study:

• To develop a novel Salmonella vector system for targeted delivery of oncolytic viruses (OVs) to solid tumors.
• To evaluate the efficacy and immunomodulatory effects of bacterial delivery of H-1 parvovirus (H-1PV) in preclinical cancer models.

Main Methods:

• Engineered Salmonella typhimurium to serve as a vector for delivering virus-encoding plasmids (VDS).
• Administered VDS intravenously and assessed tumor colonization, cancer cell invasion, and viral replication.
• Evaluated tumor reduction, survival rates, immune cell responses (dendritic cells, CD8 T cells, macrophages), and splenocyte formation.

Main Results:

• Intravenous VDS administration was safe, demonstrating significant tumor colonization (50 million-fold higher than clearance organs).
• Bacterial delivery of H-1 parvovirus markedly reduced hepatocellular and pancreatic tumors, increased survival, and prevented tumor re-implantation.
• VDS treatment enhanced immune responses, including increased dendritic cells, CD8 T cell infiltration, and polarized macrophages, outperforming direct H-1PV injection.

Conclusions:

• Combining bacteria and OVs via VDS is a safe and effective strategy for targeting solid tumors.
• This approach activates the immune system, generates robust antitumor immunity, and offers a promising platform for cancer therapy.
• Bacterial delivery of OVs represents a significant advancement over direct viral injection, improving therapeutic outcomes.