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Commercial feasibility of a therapeutic approach to cancer based on ‘LEGO’ antibody recruiting glycodendrimers

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).

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Topic(s)

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ERC-POC - Proof of Concept Grant

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Call for proposal

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(opens in new window) ERC-2020-PoC

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Host institution

UNIVERSITE GRENOBLE ALPES
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
621 AVENUE CENTRALE
38058 GRENOBLE
France

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Region
Auvergne-Rhône-Alpes Rhône-Alpes Isère
Activity type
Higher or Secondary Education Establishments
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Total cost

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