Project description
LEGO-based immunotherapics against cancer
Cancer incidence is rising globally, and despite advances in treatments, there are many side effects that hamper their effectiveness. Immunotherapy has emerged as a promising anticancer strategy, but efficacy and toxicity issues remain to be addressed. The EU-funded THERA-LEGO project will build on previous experience to produce antibody recruiting glycodendrimers (ARGs) using a molecular LEGO approach capable of binding endogenous antibodies and redirecting them against tumours. ARGs form ternary complexes with cancer cells, causing cell death. Scientists will screen these synthetic ARG structures in humanised models of cancer before proceeding with clinical development.
Objective
Cancer remains a major cause of mortality worldwide, with projections estimating that 40% of population will be diagnosed with a form of cancer during their lifetime. Despite significant progress in treatment modalities, current therapeutic regimens are still deficient due to intolerable side effects, while stray cancer cells often escape destruction. Immunotherapy-based approaches certainly represent the most promising alternatives in this area although very limited approaches are available. In addition, major issues remain to be addressed such as the lack of efficiency and autoimmune toxicity for a large population of patients. In the ERC Consolidator grant “LEGO”, we have demonstrated that fully synthetic structures with unprecedented combinations have immunological properties against cancers. We have developed a “molecular LEGO” approach to construct Antibody Recruiting Glycodendrimers (ARGs) embedded with key structural parameters and capable of redirecting endogenous antibodies present in the human bloodstream against tumors without preliminary immunization. Among a variety ARGs, we have identified two lead compound that: 1/ recruit natural Abs with a cluster of oligosaccharides; 2/ target cancer receptors with a cluster of peptides; 3/ promote the formation of a ternary complex between natural Abs and cancer cells; 4/ promote up to 60% of cytotoxicity towards cancer cells in vitro. Within THERA-LEGO, we aim to investigate the commercial feasibility and the in vivo properties of our lead compounds (toxicity, stability, biodistribution, pharmacokinetics/dynamics, immunogenicity) in humanized mice models, to facilitate the transfer of the technology to a company and the initiation of clinical development. The work to be done in this project will advance our assets from a Technology Readiness Level (TRL) of 3 to 5 and will enable us to create an exploitation strategy (relying either on commercialization through own spin-off or licensing to a pharma company).
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- social sciencessociologydemographymortality
- medical and health sciencesbasic medicineimmunologyimmunisation
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics
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Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
38058 Grenoble
France