Periodic Reporting for period 2 - GlycoTherapy (New frontiers in advanced glycotherapy for cancer)
Período documentado: 2024-06-01 hasta 2025-11-30
Cancer remains a major cause of death despite the phenomenal progress in current immunotherapy. This kind of treatment aims to boost host immune response relying on specificity of antibodies and T cells, and their ability to distinguish between cancer and normal cells. The three main cancer immunotherapies are cellular therapeutics, immune checkpoint blockade and therapeutic cancer vaccines, but those have only limited success, mainly due to difficulties in identifying target antigens. Carbohydrate chains (glycans) ubiquitously occupy the surface of cells, but cancer cells express aberrant glycans. The presentation mode of glycans and their heterogeneity affect their immune recognition, but the fundamental understanding of how these factors contribute to efficient cancer therapy in vivo has not been defined systematically. The primary objective of this proposal is to design a comprehensive novel cancer immunotherapy approach targeting glycan-neoantigens. We use an innovative interdisciplinary approach that integrates glycobiology, immunology, biochemistry, nanotechnology, with cutting-edge technologies, to design and fully investigate new frontiers in cancer ‘GlycoTherapy’ in vivo. Our discovery line is aimed to yield valuable translational tools and knowledge in diverse research fields. Successful comprehensive understanding of glyco-immunotherapy will provide a platform to design, generate and validate potent novel cancer theranostics that would fit treatment in humans. It employs established systems side-by-side with state-of-the-art technologies, including glycan microarrays.
Using our modular platform approach, we have been able to establish an optimized therapeutic active cancer vaccine that shows highly efficeint killing in vivo in a human-like mouse model, with full mechanistic insights into effects of adjuvant, immune cells involvement, and the developed humoral responses repertoire and kinetics analyzed by glycan microarray and other advanced techniques. This platform is now focused at further investigation into the factors that affect glyco-cancer vaccine efficacy, and the tools that can be extracted from such potent immune responses.
Our discovery line is based on a two-arms modular platform to study both engineered carbohydrate-cancer vaccines and T cells and their combined effects with checkpoint blockade on therapeutic glycan immune recognition in mouse models. Both efficacy and immune responses will be evaluated in detail by systematic characterization of immune cell by NGS and humoral responses by glycan microarrays to track response repertoire and kinetics throughout the various designed and optimized treatment regimes, and would yield valuable tools and knowledge in diverse research fields.