Next-IO™ CD47 × CD19 Therapeutic Bispecific Antibody Program

About This Program

This program aims to develop CD47 × CD19 therapeutic bispecific antibody for immuno-oncology.

CD47 is a protein that up-regulated in many cancers as a way to escape immune surveillance. "Don't Eat Me" CD47 signal allows healthy cells to escape the phagocytosis by macrophages and other innate immune cells. This cell-clearance mechanism is mediated by interacting CD47 on target cells with signal-regulated protein alpha (SIRPα) in bone marrow cells. Because CD47 is widely expressed in the immune system, the use of anti-CD47 therapeutic mAbs alone is not efficient. In some extreme cases, this inability may cause unfavorable pharmacokinetic characteristics or chronic toxicity, endangering patients’ systems, To overcome this, we propose an anti-CD47/CD19 bispecific antibody to tamper the blockade of CD47-SIRPα interaction in B cells.

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.

Highlighted Functions:

CD47 blockade increases phagocytosis of tumor cells in vitro and enhances tumor therapy in many human xenograft models.
The "Don't Eat Me" CD47 signal counteracts the effective "eat me" signal produced by phagocytosis-activated receptors, such as the Fc-gamma receptor, complement receptor or low-density lipoprotein receptor-related protein 1 (LRP1).
CD47 is overexpressed in most blood and solid tumors and particularly high in cancer stem cells (CSC).
Recently, CD47 neutralization has been shown to promote the development of anti-tumor adaptive T cell responses.

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

CD47 × CD19 in Cancer Studies

Here are some published data about CD47 × CD19 working as a potential target for cancer immunotherapy.

The anti-CD47/CD19 bispecific antibody (B6H12) shows a robust effect on tumor growth.

CD47 × CD19 Therapeutic Bispecific Antibody Program (Dheilly, 2017)

Combination of CD47/CD19 biAb (biAb2) and PD1/PD-L1 checkpoint blockade shows greater anti-tumor efficacy.

CD47 × CD19 Therapeutic Bispecific Antibody Program (Dheilly, 2017)

Ongoing Clinical Trials

According to a recent report published in February 2019, when entering clinical phase I trial, anti-CD47 / CD19 bispecific antibodies developed by TG Therapeutics had a relapse from refractory B-cell lymphoma. So far, this is the only case of using CD49/CD19 BiAb in clinical settings.
We believe the dual-targeting strategy can provide further insights into tumor immunotherapy, which allows us to fight cancer more efficient. In an effort to optimally leverage CD47 × CD19-mediated immune response, our next-generation CD47 × CD19 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.

CD47 × CD19 Therapeutic Bispecific Antibody Program

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop CD47 × CD19 Dual-Targeting 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

Oldenborg, P.A. CD47: a cell surface glycoprotein which regulates multiple functions of hematopoietic cells in health and disease. International Scholarly Research Notices. 2013, 2013.
Dheilly, E.; et al. Selective blockade of the ubiquitous checkpoint receptor CD47 is enabled by dual-targeting bispecific antibodies. Molecular Therapy. 2017, 25(2): 523-533.

For Research Use Only | Not For Clinical Use