Next-IO™ TGF-β × PD-L1 Bi-Functional Therapeutic Fusion Protein Program

About This Program

This program aims to develop TGF-β × PD-L1 bi-functional therapeutic fusion protein for immuno-oncology.

Rationale to develop the program:

• PD-L1 and TGF-β are key biocompound involved in independent and complementary immunosuppressive pathways, respectively.
• PD-L1 and TGF-β play roles in tumor cells’ intrinsic and extrinsic functions and their combined approach may enhance anti-tumor activity.
• Bispecific fusion proteins of TGF-β × PD-L1 work better to target tumor cells than non-tumor cells.

In summary, combining therapy of TGF-β with PD-L1 highlights a new outlook in cancer immunotherapy.

TGF-β PD-L1

Programmed death ligand 1 (PD-L1) is a key component in the immunosuppressive network, utilizing by tumors to inhibit T cell-mediated anti-tumor immune responses. Increased expression of PD-L1 in tumors associated with poor clinical outcomes. Although generally, antibodies against PD-L1 show a good clinical activity, patients who respond to PD-1 / PD-L1 therapy seems limited. Therefore, there is an increasing need to quantify the objective response rate. One strategy is to combine PD-L1 / PD-1 with other immunoreagents.

TGF-β, a growth factor highly expressed in many tumor types, promotes tumor progression and evasion through its effects on the innate and adaptive immune system. TGF-β signals tumor progression modification, angiogenesis, and epithelial-mesenchymal transition induction (EMT) through the stromal in the tumor.

With that being said, we believe the dual-targeting of PD-L1 and TGF-β can represent a reasonable therapeutic strategy in the field of cancer research.

TGF-β × PD-L1 in Cancer Studies

Here are some published data about TGF-β × PD-L1 working as a potential target for cancer immunotherapy.

• The TGF-β x PD-L1 fusion protein (M7824) inhibits tumor growth.

(Lan, 2018)

Ongoing Clinical Trials

• Currently, only one bispecific anti-TGFβ × PD-L1 fusion protein (named M7824) is undergoing clinical phase I trial. With accumulated preclinical data, synergistic anti-tumor effects of this bispecific combination are further clarified. We believe this novel dual-targeting combination will provide insight into the solid tumor.
• In an effort to optimally leverage TGF-β × PD-L1-mediated immune response, our next-generation TGF-β × PD-L1 targeted fusion protein program attempts to explore the optimal combination strategy - that is, how to exert the best anti-tumor effect while TGF-β × PD-L1 is synergistically expressed.

Program Planning and Management

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 TGF-β × PD-L1 Bi-Functional Fusion Protein 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 chance to succeed. Look forward to cooperating with you in the near future.

Reference

• Lan, Y.; et al. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β. Science Translational Medicine. 2018, 10(424): eaan5488.

For Research Use Only | Not For Clinical Use