Interleukin-12 (IL-12) is recognized for its ability to enhance anti-
tumor immunity by stimulating T cell differentiation and cytotoxicity among other immune functions. However, systemic administration of
IL-12 has faced limitations due to associated toxicities. A novel approach involves DeepTM IL-12, a fusion protein that attaches IL-12 to T cells via a Fab antibody against
CD45, aiming to concentrate its effects within the tumor microenvironment and reduce toxicity.
In this study, the safety and efficacy of Deep IL-12 were assessed using a cancer model involving CD8 PMEL T cells, which are primed with a
TCR that targets the
gp100 antigen found in B16-F10
melanoma cells. The Deep IL-12 Primed T cells were transferred into mice with established tumors and compared against treatments using standard PMEL T cells or those co-administered with systemic IL-12.
The results demonstrated that the Deep IL-12 Primed T cells significantly improved tumor inhibition and survival rates without causing overt toxicities, unlike the systemic IL-12 co-administration. These primed T cells induced sustained
IFNγ within the tumor environment, while avoiding systemic IFNγ induction which returned to normal levels quickly post-treatment. The Deep IL-12 Priming strategy also enhanced the accumulation and activity of the transferred T cells specifically in the tumor area, not affecting off-target tissues such as the spleen.
The study concludes that by tethering IL-12 to tumor-specific T cells, the Deep IL-12 Priming method enhances the therapeutic effectiveness of T cells in the tumor microenvironment while minimizing systemic exposure and toxicity, offering a promising therapeutic strategy for
solid tumors. Further toxicological evaluations of these Deep IL-12 Primed tumor-reactive T cells will be discussed, highlighting their potential benefit-risk profile.
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.
