Abstract Purpose: Bacterial cancer therapy offers a unique approach to target tumor tissues and modulate the immune microenvironment. Here, we aimed to establish an attenuated Salmonella platform capable of secreting interferon-β(IFN-β) through the flagellar type III secretion system(FT3SS) to potentiate antitumor immunity, and to evaluate its therapeutic efficacy as monotherapy and in combination with PD-L1 blockade. Methods: The attenuated Salmonella Typhimurium strain was constructed by deleting the rcsB gene from the parental BRD509 background and engineered to secrete IFN-β through the FT3SS under L-arabinose induction. IFN-β secretion was verified by Western blot and ELISA. The biodistribution of the strain was evaluated using IVIS bioluminescence imaging. The antitumor efficacy and immune activation induced by the IFN-β secreting Salmonella were assessed in CT26 tumor-bearing mice by evaluating tumor growth inhibition, apoptosis, and immune cell activation. Combination therapy with an anti-PD-L1 antibody was performed to potentiate the therapeutic effect. In addition, the in vivo safety of the strain was confirmed by monitoring serum liver and kidney function markers, body weight, and H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 272.
Kim Eunji (Fri,) studied this question.
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