Harnessing Dual Receptor Activation: The Potential of MDK-271 in Immuno-Oncology
The Fc-fusion protein, MDK-271, was developed by fusing peptide agonists MDK1169 (for IL-2/15Rβγc) and MDK1319 (for IL-7R) to separate chains of an Fc molecule. Purified and characterized using protein-A and size exclusion chromatography, MDK-271 was found to be a heterodimeric molecule with each peptide agonist attached to individual Fc-chains.
In vitro testing revealed that MDK-271 induced potent phosphorylation of STAT5 in TF-1 cells and showed additive, complementary, and synergistic effects on various lymphocyte subpopulations in human peripheral blood mononuclear cells (PBMCs). The mono-specific agonists MDK-202 and MDK-701 were found to have similar proliferative effects and signaling patterns as IL-2v and IL-7, respectively. However, the combination of both activities in MDK-271 resulted in distinct response profiles in some T-cell subsets.
The study suggests that the dual agonist activity of MDK-271 could offer advantages in anti-tumor therapeutic applications by stimulating and supporting T-cell populations more effectively than single receptor agonists. Animal studies are being conducted to further investigate these effects.
The research was conducted ethically, with the use of human PBMCs authorized under Minimal Risk Research Related Activities at the Stanford Blood Center. This work contributes to the ongoing evaluation of IL-2/15Rβγc and IL-7R as immuno-oncology targets, with the potential to advance cancer immunotherapies.
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.
