Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1-Specific VHHs.

ABSTRACT: Cytokine-based therapies for cancer have not achieved widespread clinical success because of inherent toxicities. Treatment for pancreatic cancer is limited by the dense stroma that surrounds tumors and by an immunosuppressive tumor microenvironment. To overcome these barriers, we developed constructs of single-domain antibodies (VHHs) against PD-L1 fused with IL-2 and IFNγ. Targeting cytokine delivery in this manner reduced pancreatic tumor burden by 50%, whereas cytokines fused to an irrelevant VHH, or blockade of PD-L1 alone, showed little effect. Targeted delivery of IL-2 increased the number of intratumoral CD8⁺ T cells, whereas IFNγ reduced the number of CD11b⁺ cells and skewed intratumoral macrophages toward the display of M1-like characteristics. Imaging of fl

SUBMITTER: Dougan M 

PROVIDER: S-EPMC6079513 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature