WARF TECHNOLOGIES

UW-Madison researchers developed a delivery system that is able to penetrate the ECM and shuttle surface-conjugated protein cages, composed of collagenases and anti-PD-L1 antibodies, to the PDAC tumor parenchyma. The delivery system is based on the probiotic Escherichia coli strain Nissle 1917 (EcN), which has hypoxia tropism and excellent motility. In addition, the protein cage was engineered with linkers that are susceptible to degradation by reactive oxygen species (ROS). As a result, when the EcN-protein cage enters the PDAC microenvironment, which has elevated levels of ROS, the linkers degrade resulting in the release of collagenases and anti-PD-L1. These collagenases degrade the oncogenic collagen and block the integrin α3β1-FAK signaling pathway, thereby overcoming immunosuppression and reducing the proliferation of tumor cells. The anti-PD-L1 antibodies are then able to activate infiltrating T cells for enhanced PDAC immunotherapy. 

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Tech Fields

• Therapeutics & Vaccines : Oncology