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Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice

2025.01.07

Paper Review


Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and fatal type of cancer. Immuno-therapies employing checkpoint inhibitors have shown limited efficacy in this setting, thereby underscoring an urgent need for novel therapeutic strategies.

The newly published paper in Journal of Experimental & Clinical Cancer Research titled "Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice" explores the preclinical efficacy of an innovative targeted therapy that relies on antibody-cytokine fusion proteins. In particular, it focuses on interleukin-2 (IL-2), which plays a crucial role as a driver of cell-mediated immunity and is fused to the L19 antibody. This L19 antibody has the ability to selectively bind to the extra domain B of fibronectin (EDB-FN1) that is expressed within the tumor microenvironment. This innovative fusion protein of antibody and cytokine enhances the therapeutic outcomes, thus opening new avenues for new targeted treatment strategies in pancreatic ductal adenocarcinoma (PDAC).


Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice


To confirm these findings further, researchers utilize Stereo-seq OMNI for FFPE solution to delineate the cellular heterogeneity associated with the impact of L19-IL2 and FOLFOX. Stereo-seq is also employed to identify additional immune activation markers in the L19-IL2 treatment groups. Spatial clustering of Stereo-seq OMNI data from the four cores analyzed revealed a major representation of immune activation markers for both tretments with L19-IL2 and L19-IL + FOLFOX samples. Stereo-seq heatmaps are generated to illustrate the increased infiltration of CD25+ CD122+ cells, NK cells, CD8+ T-lymphocytes, activation markers, and APC cells for the treatment with L19-IL + FOLFOX.

STOmics propels scientific discovery through innovative spatial multi-omics technology, Stereo-seq, which enables comprehensive spatial analysis of tissue microenvironment at the single-cell resolution with centimeter-level field-of-view across diverse species. Stereo-seq OMNI is an innovative spatial transcriptomics solution for FFPE samples, which provides true spatial single-cell total RNA information with accuracy and precision with the innovative 'Random Probe' design. Covering a continuous tissue area of 10mm by 10mm, Stereo-seq OMNI delivers best-in-class data and bioinformatics workflow for analyzing spatial total RNA information.

Read more about the research: https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03238-x


Find out more about STOmics Stereo-seq OMNI: https://en.stomics.tech/products/Stereo-seq-OMNI-FFPE-Solution/list.html

Journal of Experimental & Clinical Cancer Research Species·mice Organ/Tissue·pancreatic ductal adenocarcinoma