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    Area of Science:

    • Oncology
    • Microbiology
    • Immunology

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    • Chemoimmunotherapy faces challenges in tumor-specific delivery and sustained agent activation.
    • Developing integrated therapeutic strategies is crucial for effective cancer treatment.

    Purpose of the Study:

    • To engineer a bacterial platform combining enzyme/prodrug chemotherapy with immunotherapy for enhanced cancer treatment.
    • To evaluate the efficacy and mechanisms of this integrated bacterial system in a murine solid tumor model.

    Main Methods:

    • Engineered *E. coli* Nissle 1917 to express cytosine deaminase for 5-fluorocytosine conversion to 5-fluorouracil.
    • Incorporated IL-15 superagonist and PD-L1 blocking nanobody production within the bacterial platform.
    • Assessed antitumor effects and immune cell activation in the MC38 solid tumor model.

    Main Results:

    • The bacterial platform demonstrated potent antitumor activity in preclinical models.
    • Mechanistic studies revealed enhanced activation of antigen-presenting cells, T cells, and natural killer cells.
    • The therapy effectively reduced immunosuppressive cell populations within the tumor microenvironment.

    Conclusions:

    • The integrated bacterial system successfully combines enzyme/prodrug chemotherapy and immunotherapy.
    • This approach overcomes limitations of conventional therapies, offering a scalable and precise strategy for synergistic cancer treatment.
    • The engineered platform presents an improved safety profile for cancer therapy.