The
ROR1 protein is commonly found in various
cancers but not in healthy white blood cells, making it a potential target for cancer therapy. Researchers have created a DART protein that can bind to ROR1 on cancer cells and
CD3 on T cells, aiming to destroy the tumor cells. This engineered protein was modified to improve its longevity and lacks effector functions.
The protein was produced in CHO cells and purified using standard methods. Its ability to bind to both ROR1 and CD3 was tested using ELISA and SPR. The protein's effectiveness was evaluated in vitro using
lymphoma and
solid tumor cell lines and primary human T cells. Further, its ability to inhibit tumor growth was tested in mice models implanted with human T cells and cancer cells, followed by treatment with the DART protein via intravenous injection. The protein's activity was also assessed in mice with human PBMCs and established tumor xenografts after intravenous treatment.
The results showed that the DART protein binds specifically to ROR1 and CD3 antigens, and it can induce the lysis of ROR1-positive cancer cells in a dose-dependent manner. The protein also promoted T-cell activation and cytokine release in response to target cells. Importantly, it did not show activity without target cells and did not release cytokines with PBMCs alone. The DART protein demonstrated an extended half-life in mice with human
Fc receptors. In mouse studies, the growth of certain cancer cells was inhibited by the DART protein at low doses. Additionally, the molecule showed high rates of complete response in mice with established cancer cell xenografts.
The findings suggest that the DART molecule has potential as a cancer treatment and warrants further research. The study was presented at the 107th Annual Meeting of the American Association for Cancer Research by Bhaswati Barat and colleagues, detailing the development of a humanized ROR1 x CD3 bispecific DART molecule for treating various types of 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.
