Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella

Area of Science:

• Oncology
• Immunology
• Microbiology

Background:

• Combination immunotherapy improves anti-cancer efficacy but can cause immune-related adverse effects.
• Tumor-specific delivery systems can mitigate these side effects.

Purpose of the Study:

• To develop a targeted immunotherapy delivery system using engineered bacteria.
• To evaluate the efficacy of dual-payload delivery for establishing long-term antitumor immunity.

Main Methods:

• Engineered attenuated Salmonella typhimurium (SAM-FC) to release cytolysin A (ClyA) and Vibrio vulnificus flagellin B (FlaB).
• Administered SAM-FC to mice with tumors of mouse and human origin.
• Assessed tumor cell death, immune cell infiltration, and metastasis inhibition.

Main Results:

• Localized ClyA secretion induced immunogenic cancer cell death and antigen release.
• Localized FlaB secretion remodeled macrophages, inhibiting metastasis.
• SAM-FC treatment led to significant infiltration of anti-tumorigenic immune cells and activated T cells in tumors.
• Reduced immunosuppressive cells and established long-term antitumor immunity.

Conclusions:

• SAM-FC effectively delivers dual immunotherapeutic payloads for targeted cancer treatment.
• This approach reprograms the tumor immune microenvironment, activating both innate and adaptive immunity.
• SAM-FC establishes potent and durable antitumor immunity, offering a promising strategy for cancer therapy.