Immunotherapy for Pancreatic Cancer: Peptidic Targeting of a Tumor-Specific Glycan

Explore this webinar on a peptide ligand, called molecular guidance system 5 (MGS5), targeting N-glycolylneuraminic acid (Neu5Gc)-Sialyl Lewis^A in cancer, enhancing early detection and advancing liposome-based immunotherapy for pancreatic cancer. Glycosylation is a post-translation modification that is commonly altered in cancer, playing fundamental roles in cell signaling, cell migration and invasion, immune modulation and metastasis. Neu5Ac-Sialyl Lewis^A (CA19-9), part of the Lewis blood antigen family, is a well-studied blood biomarker that is Food and Drug Administration (FDA) approved for the detection of pancreatic cancer. However, its counterpart, N-glycolylneuraminic acid (Neu5Gc)-Sialyl Lewis^A, is under study in human malignancies due to the inactivation of the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene and the absence of Neu5Gc-Sialyl LewisA specific targeting molecules.

This webinar will discuss a liposome-based immunotherapy (“Targeted Antigen Loaded Liposomes” TALL) that consists of three modular components: 1) pegylated stealth phospholipid layer, 2) an encapsulated synthetic immunogenic MHC class I restricted peptide derived from the measles virus and 3) MGS5 on the external surface for tumor targeting. MGS5 binds to the surface of the cancer cells via Neu5Gc-Sialyl Lewis^A and is subsequently internalized allowing for the internalization of the liposome and the release of the encapsulated antigenic peptide. This in turn elicits a robust immune response. TALL, in combination with an anti-programmed cell death protein 1 (PD-1) inhibitor, results in a 10-fold reduction in tumor burden in mice bearing orthotopic breast and pancreatic tumors, compared to using anti-PD-1 alone.

Join this webinar to learn not only how MGS5 is a novel peptide for the detection of Neu5Gc- Sialyl Lewis^A, but it can also serve as a therapeutically relevant cancer targeting agent allowing for the delivery of therapeutics.

Speaker

Shelby Knoche, Post-Doctoral Researcher, SRI International

Shelby Knoche is a Post-Doctoral Researcher at SRI with experience in oncology and immunology research. She obtained her PhD in Cancer Biology from the University of Nebraska Medical Center, where she studied immune modulation in pancreatic cancer. In 2022 she joined the SRI team, working on SRI’s FOX Three program, focusing on using highly specific cell-binding peptides for delivery of therapeutics and SRI’s TALL immunotherapy research project, delivering antigenic liposomes to treat cancer.

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