PO-043 Development of two novel monoclonal antibodies against overexpressed antigens on pancreatic cancer cells for use in diagnosis and therapy

Material and methods The effect of NHI-Glc-2 on cell growth is tested in our primary PDAC cancer cell cultures, characterised for their hypoxic signature and LDH-A/GLUT-1 expression levels by next-generation sequencing.Inhibition of cell and tumour growth was evaluated by the SRB assay, 3D spheroid-cultures and with an orthotopic bioluminescent in vivo model.Additionally, LDH-A enzyme activity inhibition and the effect on the glycolytic rate by NHI-Glc-2 were assessed by spectrophotometry and with the Seahorse XF analyzer, respectively.Results and discussions NHI-Glc-2 is capable of inhibiting PDAC cell growth in, especially in hypoxia, in nanomolar range and shows a synergistic effect with gemcitabine.In 3D cultures NHI-Glc-2 disrupts spheroid integrity, and preliminary in vivo studies show promising results.Conclusion Lactate dehydrogenase A is a viable target in PDAC, and the novel LDH-A inhibitor showed improved pharmacological effect in normoxic and hypoxic PDAC cells compared to NHI-1 and NHI-2.Moreover, this compound displays a synergistic cytotoxic activity with gemcitabine, offering an innovative tool in hypoxic tumours.