About This Program

This program aims to develop anti-MSLN therapeutic fusion protein for immuno-oncology.

Rationale when developing the program:

• Mesothelin (MSLN), a 40 kDa glycosyl-phosphatidylinositol-linked (GPI) membrane glycoprotein, plays roles in cell survival, proliferation, tumor progression, and compliance.
• In the norm, MSLN is restrictedly expressed on mesothelial cells lining the peritoneum, pericardium, and pleura.
• MSLN is overexpressed in several cancers, such as mesothelioma, pancreatic cholangiocarcinoma, ovarian cancer, and lung cancer. Both are characterized by invasive phenotype and poor prognosis.
• In the context of tumors, MSLN promotes cancer cell survival, proliferation and migration/invasion, and drug resistance through the Wnt/NF-κB/PI3K/Akt signaling pathway.

Given the above findings, we believe the novel fusion protein targeting MSLN will be a promising field for next-generation cancer therapy.

MSLN

Although its biological function is not fully understood, the cancer-specific expression of MSLN makes it a potential therapeutic target to be researched in tumor studies. Currently, more research is still needed to verify its role in tumor metastasis.

Some highlighted data that have been verified:

• MSLN binds to the ovarian cancer antigen CA-125, which is believed to contributes to the peritoneal spread of ovarian tumor cells.
• Bispecific antibodies targeting MSLN and FcγRIII (CD16) showed great anti-tumor efficacy in a TNBC xenograft mouse model.
• In a mouse model with pancreatic cancer, MSLN overexpression promotes metastasis and proliferation of tumor cells.

MSLN in Cancer Studies

Here is a schematic model showing the scFvMTBHsp70 fusion protein binding to MSLN in tumor cells.

(Yuan, 2014)

Ongoing Clinical Trials

• Currently, NO anti-MSLN fusion protein is being evaluated in a clinical trial. Our program will be the pioneer in the field.
• In an effort to optimally leverage MSLN-mediated immune response, our next generation of MSLN targeting treatment attempts to explore combination therapy trials by involving other immunomodulatory agents.

Program Planning and Management

Creative Biolabs has 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 MSLN therapeutic fusion protein program. Our scientists are dedicated to bringing together 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 advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.

Reference

• Yuan, J.; et al. A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma. Journal of hematology & oncology0. 2014, 7(1): 1-14.

For Research Use Only | Not For Clinical Use