Dual Antagonism of GMI-1757: Enhancing Anti-PD-L1 Therapy in Pancreatic Cancer

The study explores the effects of a dual-targeting glycomimetic antagonist, GMI-1757, combined with anti-PD-L1 therapy on pancreatic tumor progression in mice. An orthotopic pancreatic carcinoma model was utilized, where mice were treated with either a control solution or GMI-1757, followed by anti-PD-L1 or an isotype control antibody. The experiment was divided into four groups, with different combinations of treatments. Bioluminescence imaging was employed to monitor tumor activity, and the study concluded with tissue analysis for fibrosis and immune cell infiltration.

The results indicated that mice treated with the isotype control experienced tumor growth, while those treated with anti-PD-L1 showed tumor growth arrest. Most notably, the combination of GMI-1757 and anti-PD-L1 led to tumor regression in a majority of the mice. Histopathological evaluation revealed that GMI-1757 reduced fibrosis within the tumors and enhanced immune cell infiltration. The study suggests that the dual antagonist could potentially improve the effectiveness of anti-PD-L1 therapy by reducing tumor fibrosis and increasing immune cell presence. Further research is being conducted on the synergistic effects of GMI-1757 with other immunotherapies to counteract the negative impacts of fibrosis and limited host cell infiltration on tumor response.