A Synthetic Microbial Therapy Rewires Antitumor Immunity Across Multiple Cancer Types

Area of Science:

• Microbiology
• Immunology
• Oncology

Background:

• Microbial immunotherapies offer potential against cancer but lack broad efficacy and mechanistic understanding.
• The tumor microenvironment (TME) is a key factor in cancer progression and treatment resistance.

Purpose of the Study:

• To introduce SPIKE 1.0 (S1.0), a metabolically engineered bacterium for cancer immunotherapy.
• To evaluate the efficacy, safety, and mechanisms of S1.0 in preclinical cancer models.

Main Methods:

• Metabolic engineering of bacteria to produce hydroxyindoles from tryptophan.
• Systemic administration of S1.0 in multiple murine cancer models, including humanized mice.
• Multi-omics profiling to analyze TME and immune cell changes.
• Comparison with checkpoint inhibitors and combination with chemotherapy.

Main Results:

• A single dose of S1.0 induced potent and durable antitumor responses with low toxicity.
• S1.0 enhanced inflammatory signaling, activated innate and adaptive immunity, and improved T cell function.
• S1.0 demonstrated superior efficacy to checkpoint inhibitors and synergistic effects with chemotherapy.
• Rewiring of amino acid metabolism and disruption of immunosuppressive networks were observed.

Conclusions:

• SPIKE 1.0 is a promising microbial immunotherapy for solid tumors.
• S1.0 effectively remodels the TME and enhances anti-tumor immunity.
• S1.0 represents a scalable, cost-effective therapeutic with broad translational potential.