About This Program

This program aims to develop CD47 × PD-L1 dual-targeted therapeutic fusion protein for immuno-oncology.

Rationale when developing the program:

• CD47 and PD-L1, respectively, work as key innate and adaptive checkpoints.
• CD47 and PD-L1 checkpoints on tumor cells can coordinate to suppress immune sensing.
• Bispecific fusion proteins work better when targeting tumor cells than non-tumor cells.
• Dual-targeting of both checkpoints enables phagocytosis of tumor cells, promotes antigen presentation in innate immunity, and increase tumor-specific T cell activation in adaptive immunity with low blood toxicity.

In summary, combining therapy involves CD47 and PD-L1 may highlight a new outlook in cancer immunotherapy.

CD47 × PD-L1

The programmed death-ligand 1 (PD-L1; or CD274, B7-H1) is a key anti-phagocytic signal, i.e "don't find me" signal, to the adaptive immune system. Similarly, CD47 is the key "don't eat me" signal for the innate immune system and adaptive immune response regulators. Both CD47 and PD-L1 are overexpressed on the surface of cancer cells. This can up-regulate the expression of their own regulators, therefore escaping immune surveillance.

Recent studies have shown that:

• The dual-blockage of CD47 and PD-L1 benefits the treatment of melanoma and colon cancer.
• The feasibility of co-expressing oncogenic CD47 and PD-L1 for tumorigenesis is demonstrated.

CD47 × PD-L1 in Cancer Studies

Here are some published data about CD47 × PD-L1 serving as a potential target for cancer immunotherapy.

• The CD47 x PD-L1 fusion protein inhibits tumor growth.

(Liu, 2018)

Ongoing Clinical Trials

• As far as we knew, NO bispecific anti-CD47 × PD-L1 antibody is including in the clinical trial. But accumulated preclinical data are emerging, demonstrate the synergistic anti-tumor effects of this bispecific combination of CD47 × PD-L1.
• We believe that this dual-targeting strategy will provide insights into tumor immunotherapy, which allows us to fight cancer more efficient. In an effort to optimally leverage CD47 × PD-L1-mediated immune response, our next-generation CD47 × PD-L1 targeted antibody program attempts to explore the optimal combination strategy - that is, how to exert the best anti-tumor outcome while synergistically produce CD47 × PD-L1.

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 CD47 × PD-L1 Dual-Targeted 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.

References

• Liu, X.; et al. Dual targeting of innate and adaptive checkpoints on tumor cells limits immune evasion. Cell reports. 2018, 24(8): 2101-2111.
• Liu, B.; et al. Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages innate and adaptive immune responses. MAbs. 2018, 10(2): 315-324.

For Research Use Only | Not For Clinical Use