Drug-eluting scaffold inhibited in vivo pancreatic tumorigenesis by engaging murine CCR4+CD8+ T cells

Abstract

CCL17 is well known for its ability to engage CCR4⁺CD8⁺ T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4⁺CD8⁺ T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1μm to 4μm. The in vitro study confirmed that scaffolding materials were non-cytotoxic to pancreatic cancer cells. The in vivo study showed an increased presence of murine CCR4⁺CD8⁺ T cells into the tumor mass treated with drug-eluting scaffold compared to those with non-eluting scaffold or the control groups. The weights of tumor masses were 132.04mg±12.25mg in the control group, 158.12mg±18.98mg in the NES group and 96.22mg±14.56mg in the DES group, respectively. The volumes of tumor masses were 1035.21mm³±128.97mm³ in the control group, 978.56mm³±110.19mm³ in the NES group and 634.35mm³±87.12mm³ in the DES group, respectively. Further study showed that the increased presence of CCR4⁺CD8⁺ T cells also inhibited the hepatic metastasis of pancreatic cancer cells. Our study shed a new light on the post-operative treatment of pancreatic cancer to prevent the recurrence.

Keywords: Cytotoxic T cells; Drug delivery; Immunotherapy; Pancreatic cancer.