Descrizione del progetto
Terapia cellulare mirata alla vascolarizzazione del tumore
Intervenire sulla vascolarizzazione del tumore sta emergendo come promettente strategia di trattamento anticancro. Lo scopo del progetto AngioCAR, finanziato dall’UE, è quello di sviluppare una terapia cellulare adottiva basata sulle cellule T del recettore dell’antigene chimerico (CAR, Chimeric Antigen Receptor) diretta contro i vasi di nuova formazione nei tumori solidi. Le cellule CAR T trasporteranno anticorpi contro una forma extracellulare della proteina citoscheletrica vimentina, riscontrata specificamente nei tumori. Le cellule CAR T che hanno come target la vimentina agevoleranno l’uccisione delle cellule endoteliali e aumenteranno anche l’infiammazione locale, riducendo così la soppressione immunitaria. L’approccio AngioCAR da solo o in combinazione con inibitori del checkpoint aprirà nuove possibilità per un’efficace terapia del cancro.
Obiettivo
Advances of adoptive cellular therapy and monoclonal antibodies (mAbs) have resulted in unprecedented responses in patients with malignant tumors. Due to the fact that tumor growth and metastasis depend on the formation of new blood vessels, termed angiogenesis, direct targeting of the tumor vasculature provides a universal point of engagement in the battle against cancer. The main objective of this project is the development of chimeric antigen receptor (CAR) T cell approaches to target the tumor vasculature. Although extremely effective in hematological malignancies, success of CAR T cell strategies against solid tumors is lagging behind. It is hypothesized that aiming CAR T cells towards the tumor vasculature will be effective, as (i) the target is readily accessible via the blood stream and (ii) the engineered T cells do not need to enter the immunosuppressive environment of the tumor. Vimentin, which is known as a cytoskeletal protein, was found to massively externalize from tumor endothelial cells and to become deposited in the surrounding matrix, while expression in all other cells is exclusively intracellular. Therapeutic targeting of this extracellular vimentin (eVim) with antibodies – or through vaccination – resulted in pronounced inhibition of tumor growth, in absence of toxicity. AngioCAR is a multidisciplinary project, aimed to develop CAR T cells against eVim for targeting of solid tumors. Newly developed antibodies against eVim will be expressed as the CAR to redirect T cells to the tumor vasculature. This will not only result in direct endothelial cell killing, but will also increase local inflammation and reduce immune suppression. The project also aims for testing the possible synergistic combination with checkpoint inhibitors as well. AngioCAR results have the potential capacity to open new avenues in cancer treatment in terms of enhancing specificity and efficiency.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
1081 HV Amsterdam
Paesi Bassi