About This Program

This program aims to develop an anti-folate receptor alpha (CD47) therapeutic monoclonal antibody in the immuno-oncology field.

CD47 is a SIRPα ligand and an important anti-phagocytic signal expressed on tumor cells. Studies have shown that a high level of CD47 is expressed in acute myeloid leukemia (AML) stem cells, much greater than its normal counterpart. In solid tumors, a modest increase in CD47 expression was detected and inflated transcript expression associates with poor prognosis. Clinical trials of anti-CD47 antibodies are undergoing for both solid and hematological malignancies. We are hoping, by researching the effectiveness of such a mechanism, blockade of CD47 can be used as a potential treatment for cancer.

CD47

CD47 is a membrane protein expressed in almost all cell types. Many cancers are shown to be over-activated by the CD47 signal, also named as "Don't Eat Me" signal. It can evoke immune interaction with the cellular signal receptor protein alpha (SIRPα) to prevent programmed cell removal (PCR). In particular, binding of SIRPα to CD47 promotes tyrosine phosphorylation in the cytoplasmic region of SIRPα, further producing the down-regulated signal to inhibit phagocytosis.

Fig.1 CD47 regulates phagocytosis of host cells by interacting with SIRPα. (Oldenborg, 2013)

CD47 in Cancer Studies

Here are some published data regarding CD47 work as a potential target in cancer immunotherapy.

• Anti-CD47 treatment can significantly improve the survival rate in T387 grafted mice.

(Hutter, 2019)

• Anti-CD47 antibody treatment induces remissions in ALL-engrafted mice.

(Chao, 2011)

Indications

CD47 is overproduced in tumor tissues such as ovarian, breast and lung areas, but only a little and restricted distribution in normal tissues. Using reverse thinking, we are trying to develop various programs (not limited to one specific type), in which CD47 is highly expressed, to test the efficacy of it in cancer treatment.

Ongoing Clinical Trials

• At present, several anti-CD47 therapeutic monoclonal antibodies are accessed in clinical trials. A cumulative data is coming in to support its role in immuno-oncology. However, efficacy, safety, and mechanism have not yet been determined.
• Despite this, CD47 is still a compelling target for cancer immunotherapy. In an effort to optimally leverage SIRPα/CD47 axis-based immune response, the next generation CD47 targeting treatment attempts to explore combination therapy by involving other immunomodulatory agents.

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 anti-CD47 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 to further their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

• Oldenborg, P.A. CD47: A cell surface glycoprotein which regulates multiple functions of hematopoietic cells in health and disease. In Hematology. 2013, 2013(5): 614619.
• Hutter, G.; et al. Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. PNAS. 2019, 116(3): 997-1006.
• Chao, M.P.; et al. Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer research. 2011, 71(4): 1374-1384.
• Anthony, C.; et al. Targeting folate receptor alpha for cancer treatment. Oncotarget. 2016, 7(32).

For Research Use Only | Not For Clinical Use