About This Program

This program aims to develop PAUF therapeutic monoclonal antibody for pancreatic cancer immunotherapy.

Rationale for our program:

• An initial decrease in PAUF expression was observed in the early stages of pancreatic cancer, followed by an increase in metastatic sites.
• Loss of PAUF in pancreatic cancer cell lines causes severe changes in cell phenotype and cell cycle, including tetraploids, extensive genomic alterations, micronuclei, and increased apoptosis.
• In metastatic pancreatic cancer cells, transient silencing ofPAUF is associated with decreased migration and invasion, decreased proliferation, and increased apoptosis.

These findings indicate an important role for PAUF in pancreatic cancer progression and metastasis.

PAUF

Pancreatic cancer up-regulation factor (PAUF), also known as ZG16B, was first discovered in secreted Pancreatic cancer cell secreted proteins. PAUF is highly expressed in many cancers, such as pancreatic cancer, cervical cancer, and ovarian cancer. In particular, in pancreatic cancer, PAUF promotes adhesion and enhanced the resistance of pancreatic cancer cells to anoikis by modulating Focal Adhesion kinase. PAUF interacts with the Toll-like receptor (TLR2 / 4) to activate CXCR4 and promote angiogenesis.

Fig.1 PAUF enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer. (Thyagarajan, 2019)

Recent studies have shown that:

• PAUF knockdown showed smaller size of tumor compared with NC CFPAC-1 cells in pancreatic cancer cell lines.

(Cho, 2017)

This data supports the rationale for the development of the first-in-class human PAUF Abs with an improved therapeutic index for the treatment of pancreatic cancer.

Pancreatic Cancer

• Pancreatic cancer is the most common type of gastrointestinal cancer, and its incidence is increasing in developed countries.
• The global cancer immunotherapy market is worth $58.1 billion in 2018. The expanding research of immunotherapy will become one of the important trends in the global pancreatic cancer treatment market from 2019 to 2023.
• Immunotherapy products such as immunological checkpoint inhibitors and vaccines are part of active research.
• The global pancreatic cancer treatment market research report predicts that the market will grow at a compound annual growth rate of more than 8% during the forecast period.

Ongoing Clinical Trials

• Currently, there are still NO PAUF therapeutic monoclonal antibodies entering the clinical stage.
• We believe that this novel targeting strategy will provide insights into the tumor immunotherapy, especially in the treatment of pancreatic cancer. In an effort to optimally leverage PAUF-mediated immune response, our next-IO™ PAUF targeted antibody program attempts to explore the optimal combination therapy trials by involving other immunomodulatory agents.

Program Plan

We have extensive knowledge of end-to-end program development. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop PAUF therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership together. For any partners interested in our Next-IO™ programs, Creative Biolabs welcomes collaboration.

Here are two ways for your choice, and please contact us for more details.

1) Collaborate with us and co-develop the programs from the discovery phase to IND enabling. Costs will be shared.

2) Become a licensed candidate for our programs.

With our quality control protocol and knowledge of global regulatory requirements, we can help our partners further their programs with more chances to succeed. Look forward to cooperating with you in the near future.

References

• Thyagarajan, A.; et al. Myeloid-derived suppressor cells and pancreatic cancer: Implications in novel therapeutic approaches. Cancers. 2019, 11(11): 1627.
• Cho, J.H.; et al. Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells. Oncotarget. 2017, 8(44):76398-76407.

For Research Use Only | Not For Clinical Use