On October 5, 2022 Prestige Biopharma Limited, a Singapore-based biopharmaceutical company, reported that a team of scientists at Prestige Biopharma Innovative Discovery Centre (IDC) published a study titled ‘PAUF Induces Migration of Human Pancreatic Cancer Cells Exclusively via the TLR4/MyD88/NF‐κB Signalling Pathway’ in the International Journal of Molecular Sciences (Press release, Prestige BioPharma, OCT 5, 2022, View Source [SID1234621723]).
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PAUF (pancreatic adenocarcinoma up‐regulated factor) is a novel secreted protein which is substantially expressed in pancreatic cancer cells. It is known to induce pancreatic cancer progression and metastasis. According to this study, PAUF binds directly to TLR4 (Toll‐like receptor 4), which is identified as a receptor for PAUF, on pancreatic cancer cell surfaces and promote cell migration exclusively through the TLR4/MyD88/NF‐κB pathway.
In addition, the study demonstrated that the knockout of TLR4 led to a marked decrease in the expression of PD‐L1 (Programmed Death‐Ligand 1), an immune checkpoint contributing to cancer immune escape. Accordingly, the scientists are conducting a follow-up study to confirm if combining anti-PAUF treatment with TLR4 inhibitor can enhance treatment efficacy.
The results of this study enhanced the understanding of the mechanism of PAUF‐induced tumour‐promoting effects. Furthermore, it suggests that TLR4 expression on cancer cells may be a critical biomarker for anti‐PAUF treatment, implying a potential clinical application in later phase clinical trials.
Prestige Biopharma has been developing PBP1510 (INN: Ulenistamab), a first-in-class anti-PAUF monoclonal antibody for pancreatic cancer treatment. PBP1510 been granted Orphan Drug Designation (ODD) by the European Medicines Agency (EMA), US Food and Drug Administration (FDA) and Korean MFDS. Currently, it is on Phase 1/2a clinical trial in France, Spain, and US.
Sangseok Koh, President of Prestige Biopharma IDC commented: "Through this study, we found a potential therapeutic biomarker and target for the development of effective pancreatic cancer treatment. We will keep up our research to discover and develop methods to control TLR4 expression and further improve PBP1510’s treatment effect."
Meanwhile, Prestige Biopharma IDC is also undergoing research on technology for diagnosis of pancreatic cancer by detecting PAUF in the body. IDC aims to continue its efforts to enable early diagnosis of fatal diseases as well as effective treatment through innovative drugs.