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Combinatorial Antibody Synthesis for the Discovery of New Anti-Tumour Immunomodulators

Descrizione del progetto

Una nuova tecnologia per la sintesi di anticorpi antitumorali

Il principale svantaggio dei trattamenti antitumorali è la loro mancanza di selettività, che comporta effetti collaterali significativi. Lo sfruttamento del sistema immunitario per combattere il cancro si è rivelato un approccio terapeutico promettente. Il progetto BispecificsThatClick, finanziato dall’UE, sta concentrando l’attenzione sullo sviluppo di anticorpi bispecifici diretti a due antigeni, uno sulle cellule tumorali e l’altro sulle cellule immunitarie, che porta all’efficiente eliminazione del primo. Gli scienziati hanno sviluppato una nuova metodologia per accelerare e migliorare l’efficienza della produzione di anticorpi bispecifici. La raccolta di anticorpi generata sarà soggetta a numerose analisi per stabilirne il meccanismo d’azione e l’efficacia contro il tumore.

Obiettivo

Cancer represents one of the major challenges for modern medicine as we still lack tools to selectively target malignant over healthy tissues. The main issues with state of the art anti-cancer treatments lie on their inefficiency and their associated side-effects. Improving this treatments has focused a lot of attention of the scientific community and has led to the development of new strategies. Harnessing our own immune system to fight malignant cells is one of the strategies with promising potential to improve cancer treatments, although challenges still remain. An emerging therapeutic modality to trigger our immune system against carcinogenic tissues are bispecific antibodies (bsAbs). bsAbs are the combination of two antigen binding specificities on a common scaffold. The potential of these constructs to bind to two antigens can be used to simultaneously target cancer cells and the immune cell which will effectively kill it. The problem of bsAbs is their slow and tedious production process, which is responsible for their linear development. Herein we propose a methodology to speed up and improve the efficiency of their production. Our approach will consist in using novel site-specific bioorthogonal ligation reactions to tag monoclonal antibodies (mAbs) with linkers that will serve as substrates for an inverse electron demand Diels Alder condensation. By condensation of different combinations of tagged mAbs a library of bsAbs will be assembled. The immunondulatory properties of the bsAbs will be tested in high throughput using a high content imaging platform. We will be able to select potential bsAbs for anticancer treatment from our extense library which will study in more depth using classic immunology methods to determine their mode of action and their anti tumour efficacy. The acceleration of both the synthesis and identification of relevant bsAbs for anticancer treatments would significantly increase the presence and value of this technology.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.

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Meccanismo di finanziamento

MSCA-IF-EF-ST - Standard EF

Coordinatore

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Contribution nette de l'UE
€ 212 933,76
Indirizzo
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
Regno Unito

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Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 212 933,76