Development of TACA Glycan Library and Related Glycomics Products

Project Summary/Abstract: Tumor-associated carbohydrate antigens (TACAs) are aberrantly expressed glycans associated with cancer cells, playing critical roles in cancer progression and immune evasion. Despite their potential as diagnostic and therapeutic targets, the lack of comprehensive tools to study TACA interactions has significantly limited progress in this field. This project addresses these challenges by developing the first comprehensive TACA glycan library and glycan array, integrating 58 existing TACAs with 22 newly synthesized glycans and glycopeptides for MUC16 (CA125), sTRA, and sLeA. These newly synthesized TACAs enable detailed exploration of the glycoform-specific interactions of MUC16, sTRA, and sLeA. The TACA glycan array will feature TACAs displayed at varying densities and valencies, simulating the diverse glycan presentations found on cancer cells. This innovative design allows for the systematic evaluation of TACA interactions with therapeutic antibodies, biologics, and glycan-binding proteins. By providing tools to study these interactions under biologically relevant conditions, the project aims to advance the development of TACA-targeted diagnostics and therapeutics. Phase I focuses on developing and validating the TACA library and associated array, leveraging Z-Biotech’s expertise in glycan synthesis and array fabrication. The amine-tagged TACAs, both pre-existing and newly synthesized in this project, will also support broader applications, such as conjugation to fluorescent beads for autoantibody screening. Phase II will expand the library to include over 300 TACAs and further refine the array for commercial deployment. This initiative will accelerate the discovery of new TACA-targeted diagnostic and therapeutic candidates, establish a transformative research resource, and deepen our understanding of TACA-mediated cancer biology.