A study has been conducted to develop monoclonal antibodies (mAbs) targeting
B7-H3, a protein highly expressed in various human tumors and linked to poor patient outcomes. The research team successfully created a mouse anti-human B7-H3 antibody, M30, which demonstrated antitumor properties. This antibody was then humanized into Hu-M30, and an afucosylated version,
DS-5573a, was also produced.
The DS-5573a mAb was characterized and its antitumor capabilities were tested both in vitro and in vivo. The analysis revealed that B7-H3 is broadly expressed across different
cancer cell lines and that DS-5573a can bind to the IgC1 and IgC2 domains of human B7-H3. The mAb showed significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) against cancer cell lines expressing medium to high levels of B7-H3, such as MDA-MB-231 and NCI-H322. Notably, DS-5573a induced high ADCC activity against the low B7-H3-expressing cancer cell line COLO205, while Hu-M30 had minimal effect.
Furthermore, DS-5573a was identified as a novel anti-B7-H3 antibody with the ability to mediate antibody-dependent cellular phagocytosis. In terms of in vivo antitumor efficacy, DS-5573a exhibited dose-dependent and significant tumor reduction in SCID mice bearing MDA-MB-231 tumors, which have functional natural killer cells and macrophages. However, it showed little efficacy in NOG mice, which lack natural killer cells and have diminished macrophage function.
These findings indicate that the antitumor activity of DS-5573a is mediated by effector cells and suggest that this mAb has the potential to be a promising therapeutic agent for patients with a variety of B7-H3-expressing tumors.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
