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

Descrizione del progetto

Immunoterapia antitumorale a base di LEGO

L’incidenza del cancro è in crescita a livello globale e il suo trattamento, nonostante i progressi compiuti, presenta effetti collaterali che ne ostacolano l’efficacia. L’immunoterapia si è progressivamente affermata come strategia antitumorale promettente, ma devono ancora essere risolti gli aspetti legati all’efficacia e alla tossicità. Il progetto THERA-LEGO, finanziato dall’UE, si baserà su esperienze precedenti volte a produrre anticorpi con il reclutamento dei glicodendrimeri per mezzo di un approccio molecolare di tipo LEGO, in grado di legare gli anticorpi endogeni e reindirizzarli contro il tumore. I glicodendrimeri formano complessi ternari con le cellule tumorali, provocando la morte cellulare. Gli scienziati del progetto esamineranno queste strutture sintetiche di glicodendrimeri nei modelli umanizzati del cancro prima di procedere nello sviluppo clinico.

Obiettivo

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).

Campo scientifico (EuroSciVoc)

Programma(i)

Argomento(i)

Meccanismo di finanziamento

ERC-POC - Proof of Concept Grant

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Invito a presentare proposte

(si apre in una nuova finestra) ERC-2020-PoC

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Istituzione ospitante

UNIVERSITE GRENOBLE ALPES
Contributo netto dell'UE
€ 150 000,00
Indirizzo
621 AVENUE CENTRALE
38058 Grenoble
Francia
Regione
Auvergne-Rhône-Alpes Rhône-Alpes Isère
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)