The
GITR co-stimulatory receptor is crucial for initiating immune responses in lymph nodes and sustaining them in
tumor tissues. It enhances anti-tumor T cell activation and survival upon binding to its ligand and diminishes the inhibitory function of Treg cells, thereby boosting the immune response against tumors. A novel technology named
HERA has been developed to target the
TNF-receptor superfamily, creating fully human hexavalent fusion proteins that are potent agonists with high clustering capacity. This study presents the in vitro and in vivo characteristics of newly developed hexavalent HERA-GITRL constructs.
In vivo stability was evaluated using serum samples from CD1-mice in a pharmacokinetic study, with drug levels measured via ELISA. Immune cells from healthy donors were used for in vitro testing, where they were analyzed by flow cytometry after isolation. Cells were then exposed to various HERA-
GITRL constructs and anti-
CD3 in culture media. The activation and memory markers on T cells, proliferation rate, and cytokine levels were assessed.
The study found that slight modifications resulted in three distinct HERA-GITRL drug candidates with unique pharmacokinetic profiles and stability in mice, with a terminal half-life ranging from 61.7 to 200.6 hours. HERA-GITRL significantly increased the expression of activation markers on pan T cells and naive CD4+ T-lymphocytes, along with their proliferation and memory formation. Additionally, there was an elevated level of intracellular
TNF-α and
IFN-γ in naive CD4+ T-lymphocytes, which was further enhanced by HERA-GITRL.
The conclusion is that HERA-GITRL constructs show excellent in vivo stability and their capacity to stimulate the proliferation and activation of naive CD4+ T cells, as well as induce memory formation, makes them promising candidates for cancer immunotherapy.
The study was presented at the American Association for Cancer Research Annual Meeting in 2017, and the abstract was published in the Cancer Research journal.
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.
