The abstract discusses the development of a new type of immunocytokine for
cancer treatment.
IL-2 therapy has been shown to be effective but is associated with significant side effects. Previous attempts to create IL-2-based immunocytokines have not been successful due to issues such as high functional affinity, rapid clearance, and preferential activation of Tregs. The new immunocytokine described in this study is a monomeric, tumor-targeted version that uses a modified IL-2 (IL-2v) which does not bind to
CD25 but retains IL-2Rbg binding. This IL-2v is fused to a tumor-specific antibody with a mutated Fc-part that prevents FcgR and
C1q binding.
The immunocytokines,
CEA-IL2v and
FAP-IL2v, were produced and tested for their ability to activate immune cells without binding to CD25 or activating Tregs. They were found to activate NK cells and T cells, and to expand the CD8 T cell population in vivo. In mice, these immunocytokines showed improved safety and pharmacokinetics, with FAP-IL2v demonstrating effective tumor targeting with minimal uptake in normal tissues. The targeting was superior to that of a wildtype IL-2 immunocytokine. The efficacy of CEA- and FAP-IL2v was demonstrated in mouse models, showing an increase in survival rates.
In conclusion, the new immunocytokines show promise for the treatment of
CEA/FAP-positive tumors due to their improved safety profile, pharmacokinetics, and tumor targeting capabilities. They activate NK and T cells through IL-2Rbg, particularly when immobilized in the tumor microenvironment. The study supports further investigation into these immunocytokines for cancer immunotherapy.
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.
