The abstract discusses the use of autologous T cells modified to carry
CD19-specific chimeric antigen receptors (CAR-T) for treating
B cell cancers. It notes the difficulty of applying CAR-T therapy to targets other than CD19 due to challenges in managing CAR-T cell activity and the scarcity of antigens unique to malignant cells. The
CD123 antigen, linked to
leukemia, is highlighted as a potential target for immunotherapy but is also expressed in healthy stem cells and blood vessels, making it a risky target.
A new platform called UniCAR has been introduced to address these issues. It is composed of two parts: a non-reactive, inducible second-generation CAR designed for safe manipulation (UniCAR-T), and soluble targeting modules that activate UniCAR-T cells in a target-specific way.
The study presents data on the use of
UniCAR-T with a CD123-specific targeting module (TM123) for treating
acute leukemia. It shows that UniCAR-T cells, when redirected by TM123, can effectively eliminate CD123-positive leukemic cells both in vitro and in vivo. The activation and response of these cells are strictly controlled, and they exhibit comparable anti-leukemic effects to traditional CAR-T cells.
Importantly, UniCAR-T cells are able to distinguish between high-expressing malignant cells and low-expressing healthy cells, reducing toxicity to stem cells. A new targeting module with a bound
4-1BB ligand has been created to enhance CAR-T activity at the site of the
tumor. This module, TM123-4-1BBL, showed specific binding to both 4-1BB and CD123-positive cells and improved the killing capability of UniCAR-T in tumor eradication models.
The study concludes that UniCAR-T cells maintain high efficacy against leukemia while providing a mechanism for immediate control, enhancing safety and versatility. The ability to switch between different targeting modules with varying plasma half-lives allows for personalized treatment strategies and minimizes adverse effects.
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.
