Descrizione del progetto
Semplificare e accelerare il processo di scoperta degli anticorpi monoclonali
Il sistema immunitario si affida in larga misura agli anticorpi, cellule immunitarie specializzate nella ricerca di specifici marcatori chiamati antigeni sulle cellule considerate «minacce». Gli anticorpi monoclonali (mAb) sono proteine create dall’uomo che agiscono analogamente agli anticorpi umani. In commercio ne sono stati approvati oltre 100, diventati strumenti essenziali a disposizione dei medici; tuttavia, il processo inteso a scoprirne di nuovi è attualmente molto inefficiente e dispendioso in termini di tempo, denaro e sforzi, nonché dipendente dall’impiego di mammiferi. Concentrandosi sul cancro, il progetto ALADDIN, finanziato dal CEI, snellirà drasticamente questo processo di scoperta. A tal fine, integrerà diversi strumenti, ovvero cellule batteriche con una libreria universale di Ab a singolo dominio chiamati nanocorpi, strumenti di intelligenza artificiale, metodi di microfluidica, un modello tumorale del pesce zebra e modelli matematici.
Obiettivo
Since the approval of the first monoclonal antibody (mAb) 30 years ago, therapeutic mAbs and Ab-derived molecules have come to dominate the biologics market. Currently, +100 Abs are in clinical use for different diseases, out of which +30 mAb target cancer. Despite the huge market potential, multiple and complex steps make the therapeutic Ab discovery process long, expensive, laborious, and inefficient. These steps include target identification, animal immunization, Ab selection and engineering, humanization and preclinical validation. All these are not integrated, costly, require large equipments and facilities, and are highly dependent on experimental animals (mostly mammals, including genetically modified mice), both for immunization and for preclinical validation of the therapeutic Ab candidates.
ALADDIN project emerges to bring to the market a novel AcceLerAteD DIscovery Nanobody platform that will increase the efficiency of therapeutic Ab discovery and preclinical validation for human cancer by: 1) integrating selection and in vivo affinity maturation of Abs in bacterial cells holding an universal library of single domain Abs (nanobodies, Nbs) that fully eliminates animal inmunization; 2) using in silico Artificial Intelligent (AI) tools for structure-based epitope mapping, AI-guided affinity maturation, and Nb humanization; 3) developing cost-effective miniaturized microfluidic-based devices for in vitro Ab selection from bacterial cultures; 4) accelerating Ab validation with a fast non-mammalian in vivo model for preclinical testing based on patient-derived tumor xenografts in zebrafish larvae; 5) impacting target and Ab validation with dynamic mathematical models to extract clinical and efficacy data of the Ab candidates. These ambitious goals will be possible through the multidisciplinary ALADDIN consortium, formed by eight partners with complementary skills.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Invito a presentare proposte
HORIZON-EIC-2023-PATHFINDEROPEN-01
Vedi altri progetti per questo bandoMeccanismo di finanziamento
HORIZON-EIC - HORIZON EIC GrantsCoordinatore
28006 Madrid
Spagna