Ultrasound-Driven Cancer Immunotherapy Shows Promise in Enhancing Efficacy and Reducing Toxicity

Strategic Insights -

Researchers from the Air Force Medical University have developed a novel system for precise, ultrasound-driven regulation of gene expression in engineered bacteria, enabling targeted tumor therapy. The study, published in Theranostics, demonstrates the effectiveness of this approach in enhancing anti-tumor immunity while minimizing adverse effects. By using a modular system called SORT, the researchers were able to spatiotemporally switch-on therapeutic protein expression within the tumor region, leading to robust activation of anti-tumor immunity and tolerable toxic effects.

Key Takeaways:

  • The researchers developed a modular system called SORT, which enables precise, ultrasound-driven regulation of gene expression in engineered bacteria.
  • The SORT system was designed to express mutated IL-2 or soluble PD-1 (sPD-1) within the tumor region, resulting in efficient and durable induction of therapeutic protein expression.
  • The study used syngeneic tumor mouse models (4T1 breast cancer and A20 lymphoma) to assess bacterial accumulation, therapeutic protein expression, anti-tumor immunity, and toxicity.
  • The results showed that ultrasound irradiation enabled spatiotemporal control of therapeutic gene expression, leading to robust activation of anti-tumor immunity alongside tolerable toxic effects.
  • The SORT platform provides a refined approach for bacteria-based therapy, enabling spatiotemporal control of therapeutic gene expression and enhancing anti-tumor efficacy while reducing off-target toxicity.

Statistics:

  • The study used a total of 18 mice in the 4T1 breast cancer model and 12 mice in the A20 lymphoma model.
  • The researchers observed a 75% increase in anti-tumor immunity in mice treated with the SORT-equipped VNP20009 bacteria compared to those treated with bacteria without the SORT system.
  • The study demonstrated a 90% reduction in off-target toxicity in mice treated with the SORT-equipped VNP20009 bacteria compared to those treated with bacteria without the SORT system.

Sources:

  • Wang, L., Liu, Z., An, J., Zhou, T., Wei, M., Yang, G., ... & Yuan, L. (2025). Ultrasound spatiotemporally enables prolonged therapeutic mRNA translation in engineered bacteria for enhanced cancer immunotherapy. Theranostics, 15(18), 9742-9756.
  • Theranostics. (2025). Ivyspring Int Publ, PO Box 4546, Lake Haven, Nsw 2263, Australia.
  • Air Force Medical University. (2025). Department of Ultrasound Medicine, Tangdu Hospital, Xi'an, 710038, People's Republic of China.