Transient and Local Expression of Chemokine and Immune Checkpoint Traps To Treat Pancreatic Cancer.

ABSTRACT: Pancreatic tumors are known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (K_d = 4.1 and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and intravenously injected to mice bearing orthotopic pancreatic cancer. Expression of traps was mainly seen in the tumor, and secondarily, accumulations were primarily in the liver. Combination trap therapy shrunk the tumor and significantly prolonged the host survival. Either trap alone only

SUBMITTER: Miao L 

PROVIDER: S-EPMC5961942 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature