Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase PIN1, whose overexpression in CAFs hasnt been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective PIN1 inhibition in CAFs on pancreatic cancer, we formulate DNA-barcoded micellular systems (DMS) encapsulating PIN1 inhibitor. DMS functionalized with CAFs-targeting antibodies (antiCAFs-DMS) can selectively inhibit PIN1 in CAFs of the tumor, leading to efficacious but temporal tumor inhibitions. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to antiCAFs-DMS and thus prepare the bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT shows its potent capacity to eradicate pre-established subcutaneous and orthotopic pancreatic cancer on mice.