Technology/ Title:Development of Anti-Mesothelin x CD3 BsAb for Mesothelin+ Cancer Therapy

Summary of Invention
Asymmetric IgG-like bispecific antibody (BsAb) is the trend of next generation antibody drug development. However, the mispairing issue between light chains and heavy chains is the bottleneck of this technology. DCB has developed an asymmetric anti-mesothelin x CD3 BsAb and overcome this technological hurdle. The BsAb targets the mesothelin-overexpressing cancer cells such as pancreatic cancers, ovarian cancers, and mesotheliomas. Subsequently, it recruits and activates the T cell for cancer cell killing. The T cell activation is highly dependent on the presence of the cancer cell which elevates the safety profile of this anti-cancer drug. Its efficacy has been demonstrated and is better than its parental monoclonal antibody and fragment BsAb in the pancreatic cancer xenograft animal model. The BsAb possesses low immunogenicity property, and the production yield of its CHO-S stable clone is comparable to its parental mAb.

Advantages when compared to the existing technologies
1. Correct light chain and heavy chain pairing.
2. Longer half-life.
3. Target cancer cell-dependent T cell activation.
4. Better anti-cancer efficacy compared to the short half-life fragment BsAb and its parental monoclonal antibody.
5. High production yield comparable to its parental mAb.
6. Low Immunogenicity in rodent.