Programmable Encapsulation Enables On-Demand Proliferation of Therapeutic Bacteria for Potent Cancer Immunotherapy

Area of Science:

• Biotechnology
• Microbiology
• Cancer Therapy

Background:

• Engineered bacteria offer therapeutic potential but face challenges in clinical safety and delivery.
• Existing bacterial therapies can cause adverse immune reactions and uncontrolled proliferation in healthy tissues.

Purpose of the Study:

• To develop a programmable encapsulation technology for engineered bacteria to improve biosafety and targeted delivery.
• To create a bacterial therapeutic system that modulates the tumor microenvironment and enhances anti-tumor immunity.

Main Methods:

• Formulation of engineered Escherichia coli Nissle with a thin layer of cross-linked polymers for encapsulation.
• Engineering bacteria to convert tumor ammonia to L-arginine and secrete soluble programmed cell death protein 1 (sPD-1).
• Utilizing matrix metalloproteinase-2 (MMP-2) in tumors to trigger bacterial release and local proliferation.

Main Results:

• The encapsulation technology reduced bacterial immunogenicity and restricted proliferation in healthy organs.
• Encapsulated bacteria successfully converted tumor ammonia to L-arginine and secreted sPD-1 within the tumor microenvironment.
• Controlled bacterial release and proliferation in tumors led to L-arginine-mediated immune modulation and PD-L1 blockade, initiating anti-tumor immune responses.

Conclusions:

• The programmable encapsulation platform effectively addresses safety and delivery challenges for live bacterial therapeutics.
• This technology broadens the clinical application prospects of engineered bacteria in cancer treatment.
• The developed system demonstrates a novel strategy for localized tumor treatment through engineered bacteria.