Summary

Pancreatic cancer generally expresses high level of PAUF (pancreatic adenocarcinoma upregulated factor), a protein that drives cancer cells to spread through blood flow and to escape immune recognition. PBP1510 specifically binds to PAUF and exerts anti-metastasis and immune modulation effects.

Mechanism of Action

PAUF causes vascular leakage through binding to CXCR4 receptor on cancer cells, allowing cancer cells to escape blood vessels. This is how metastasis begins.
PAUF acts as an immune modulator: (1) PAUF binds to TLR4 receptor on monocyte and induces M2 macrophage polarization. (2) PAUF binds to TLR4 receptor on MDSCs (myeloid-derived suppressor cells) and activates MDSCs. Both M2 and MDSC suppress anti-tumor functions of cytotoxic T cells, leading to immune evasion of cancer cell.


Publication

[1] PAUF enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer. Oncotarget (2016).

[2] A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis. Biochem Biophys Res Commun (2014).

[3] PAUF, a novel endothelial activator, promotes angiogenesis and vascular permeability. Oncogene (2013).

[4] PAUF promotes metastasis by regulating TLR/CXCR4 activation. Oncogene (2011).

[5] PAUF, a novel up-regulated secretory protein in pancreatic ductal adenocarcinoma. Cancer Sci  (2009).