Glycopeptide Antigen-bearing Nanoparticles for Passive and Active Antitumor Therapy for Pancreatic Cancer

Abstract public domain (NIH RePORTER)

This project has made several strides since the last annual report. We have been studying a antibody, F5, that we developed and commercialized as a tumor-selective mAb that binds mostly to pancreatic ductal adenocarinomas (PDACs). It was raised to a protein called Mucin-4 (MUC4) which is overexpressed exclusively on PDACs and not on normal pancreatic cells. We set out to prove this antibody can distribute to MUC4-positive pancreatic tumors in vivo. We proved this in models of PDACs in the flanks of mice and showed that it bound MUC4+ and NOT MUC4- tumors. We subsequently designed and developed a novel antibody drug conjugate (ADC) and proved selective cytotoxicity to MUC4+ cells . All this lead to a proposal being awarded to work with teh Center for Advanced Preclinical Research (CAPR) here at NCI to develop this therapy in Patient-derived xenograft (PDX) models in mice. This again proved successful and we went on te devleop a Chimeric Antigen Receptor T-cell (CAR-T) from a single chain variable fragment of the F5 mAb. This proved successful aga, and cytotoxicity studies are now in progress to assess the translational capabilities of this CAR-T cell. In addition, we have prepared a vaccine platform prepared from gold nanoparticles coated with beta-1,3 glucans, which are ligands for C-type lectin receptors on dendritic cells, with various glucans types to assess the enhanced activity of any of these new constructs.