Boarding Oncolytic Viruses onto Tumor-Homing Bacterium-Vessels for Augmented Cancer Immunotherapy

Area of Science:

• Oncology
• Virology
• Immunotherapy
• Biotechnology

Background:

• Oncolytic viruses (OVs) show promise in cancer therapy due to their ability to induce systemic immune responses.
• Clinical application of OVs is limited by poor tumor enrichment and insufficient immune activation.

Purpose of the Study:

• To develop a bacteria-assisted delivery system for oncolytic adenoviruses (OAs) to enhance tumor targeting and cancer immunotherapy.
• To evaluate the efficacy of liposome-cloaked OAs conjugated onto tumor-homing Escherichia coli (E. coli-lipo-OAs) in a preclinical cancer model.

Main Methods:

• Conjugation of liposome-cloaked oncolytic adenoviruses (OAs) onto tumor-homing Escherichia coli BL21 to create E. coli-lipo-OAs.
• Administration of E. coli-lipo-OAs via intravenous injection in a non-small cell lung tumor model.
• Quantification of OA enrichment in tumors and assessment of antitumor immune responses in vivo.

Main Results:

• E. coli-lipo-OAs demonstrated over a 170-fold increase in OA enrichment within non-small cell lung tumors compared to bare OAs administered intravenously.
• Intravenous administration of E. coli-lipo-OAs significantly enhanced antitumor immunity.
• The enhanced immunity was attributed to bacterial-viral-augmented immune responses.

Conclusions:

• Bacteria-assisted targeting using self-driving microbe vehicles represents a potent strategy for systemic delivery of OVs.
• This approach significantly improves tumor enrichment and enhances antitumor immunity, paving the way for advanced cancer biotherapeutics.
• E. coli-lipo-OAs show potential as a clinical-level platform for cancer immunotherapy.