About This Program

This program aims to develop anti-GPA33 × CD3 bispecific DART protein for immuno-oncology.

Glycoprotein A33 (gpA33) is a. biomarker expressed specifically on the surface of normal human colon- and intestinal- epithelial cells. In addition, gpA33 antigen is found uniformly expressed at high levels in most (>95%) primary and metastatic human colorectal cancer (CRC), suggestinggpA33 may be an attractive target for CRC immunotherapy.

Dual-affinity retargeting (DART) technology is an antibody-based proprietary platform designing to kill TAA-expressing tumor cells using CD3 in vitro-directed redirected T cells. Here, we propose a novel DART - GPA33/CD3 DART, for patients with metastatic relapses/refractory CRC, and hopefully, provide insights into their clinical treatments.

GPA33 × CD3

GPA33 is a 43 kDa transmembrane glycoprotein, belonging to a family of adhesion molecules. Studies have found GPA33 is evenly expressed in almost all colorectal tissues (>95%) and can mediate colonic mucosal repair in an animal model with colitis. The expression of GPA33 is almost indistinguishable in all disease stages and histological differentiation. Its antigen is secreted or flowed into the bloodstream directly. These observations suggest gpA33 may be an attractive target for immunotherapy.

CD3 is a T cell co-receptor that consists of four different chains, a CD3 gamma chain, a CD3 delta chain, and two CD3 epsilon chains. These chains can bind to T cell receptors (TCR) to form a complex that later emits an activation signal in T lymphocytes.

GPA33 × CD3 in Cancer Studies

Here are some published data about GPA33 × CD3 working as a potential target for cancer immunotherapy.

• GPA33 DART (MGD007) shows robust antitumor efficacy against colorectal cancer cells.

(Moore, 2014)

Ongoing Clinical Trials

• Currently, only one anti-GPA33 × CD3 Bispecific DART Protein (called MGD007) is being evaluated in the clinical phase 1 trial. Cumulative preclinical data demonstrate its important role in cancer progression; however, safety, efficacy, and combination strategies require further confirmation. Given the importance of the T cell pathway in the treatment of cancer, we believe gpA33 DART can become a convincing target for colorectal cancer therapy.
• In an effort to optimally leverage GPA33–mediated immune response, our next generation of GPA33 DART targeting treatment attempts to explore combination therapy trials 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 year 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-GPA33 × CD3 Bispecific DART 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 to further their programs with more chance to succeed. Look forward to cooperating with you in the near future.

Reference

• Moore, P.A.; et al. Development of MGD007, a gpA33 x CD3 bi-specific DART for T-cell immunotherapy of metastatic colorectal cancer. Cancer Research. 2014, 74(19 Supplement):669-669.

For Research Use Only | Not For Clinical Use