New Frontiers Advanced Tender

Grant agreement ID 101003021Start date 1 December 2022End date 30 November 2027Overall budget 2 150 000 ObjectiveCancer remains a major cause of death despite phenomenal progress in current immunotherapy that aims to boost host immune responses of antibodies and T cells and their ability to distinguish cancer from normal cells. The three main cancer immunotherapies are therapeutic cancer vaccines cellular therapeutics and immune checkpoint blockade but those have only limited success mainly due to difficulties in identifying target antigens. Carbohydrate chains glycans ubiquitously occupy surface of cells but on cancer they are aberrantly-expressed in particular with a wide collection of sialic acid-glycans. Their antigenic complexity arise by sialic acid structure modification linkages length proteinlipid scaffolds surface organization and density. The presentation mode of glycans and their heterogeneity affect their immune recognition but the fundamental knowledge 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 propose an innovative interdisciplinary approach that integrates glycobiology immunology and nanotechnology to design and fully investigate new frontiers in cancer GlycoTherapy in vivo. 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. Efficacy will be evaluated in detail by systematic characterization of immune cell and humoral responses with cutting-edge tools including glycan microarrays to track response repertoire and kinetics. Successful establishment and in-depth understanding of these therapies will provide a platform to devise and validate potent novel glyco-cancer diagnostic tools and therapeutics and will instigate their prospective clinical translation in humans