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Updated: Jul 2, 2025

Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
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ATP-Responsive Manganese-Based Bacterial Materials Synergistically Activate the cGAS-STING Pathway for Tumor

Huang Yang1,2, Sisi Yang3, Quanshi Guo2

  • 1Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.

Advanced Materials (Deerfield Beach, Fla.)
|February 28, 2024
PubMed

Insights

Engineered bacteria release manganese ions in tumors, boosting the cGAS-STING pathway for enhanced bacterial immunotherapy against cancer. This novel approach shows promise in inhibiting melanoma and liver cancer growth.

Area of Science:

  • Biotechnology
  • Immunology
  • Materials Science

Background:

  • The cyclic guanosine monophosphate(GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is key for bacteria to activate anti-tumor immunity.
  • Current bacterial immunotherapies face limitations due to insufficient pathway stimulation.

Purpose of the Study:

  • To engineer an adenosine 5'-triphosphate (ATP)-responsive bacterial material for synergistic cGAS-STING pathway activation.
  • To enhance bacterial immunotherapy efficacy by overcoming stimulation limitations.

Main Methods:

  • Developed an ATP-responsive manganese (Mn)-based bacterial material (E. coli@PDMC-PEG).
  • Investigated the material's degradation in the tumor microenvironment, releasing Mn ions and exposing bacteria.
  • Assessed the synergistic activation of the cGAS-STING pathway by Mn ions and bacterial extracellular DNA (eDNA).

Main Results:

  • The engineered biohybrid material synergistically activates the cGAS-STING pathway.
  • Manganese ions (Mn2+) enhance cGAS sensitivity to bacterial eDNA.
  • E. coli@PDMC-PEG and VNP20009@PDMC-PEG demonstrated significant inhibition of subcutaneous melanoma in mice and in situ liver cancer in rabbits.

Conclusions:

  • The developed Mn-based bacterial material offers a promising strategy for enhancing bacterial immunotherapy.
  • This approach effectively leverages the tumor microenvironment's ATP to activate the cGAS-STING pathway.
  • Provides valuable insights for advancing bacteria-based cancer treatment.
Keywords:
ATP responsibilitycGAS‐STING pathwayengineered bacteriatumor immunotherapy

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