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Mechanical Immunoengineering for Enhanced T-cell Immunotherapy

Descrizione del progetto

Immunoterapia avanzata a base di cellule contro i tumori solidi

Le cellule T ingegnerizzate per esprimere recettori chimerici dell’antigene (cellule CAR-T) hanno mostrato risultati incoraggianti contro le neoplasie ematologiche. L’ambiente immunosoppressivo dei tumori solidi, tuttavia, impedisce alle cellule CAR-T di raggiungere il sito del tumore, rendendo necessarie strategie di potenziamento. Il progetto MechanoIMM, finanziato dall’UE, propone di sfruttare segnali biofisici e meccanici per modulare l’immunità antitumorale. I ricercatori progetteranno nanoparticelle che rispondono ai segnali meccanici dei tumori e forniranno farmaci che supportano le cellule T. Inoltre, ingegnerizzeranno cellule T in grado di discriminare fra la rigidità del tumore e i tessuti sani, migliorando così la specificità della terapia cellulare.

Obiettivo

Cancer immunotherapy harnessing the power of a patient’s immune system to fight cancer is transforming the standard-of-care for cancer. Adoptive cell therapy (ACT), a potent immunotherapy that directly infuses a large number of tumour-reactive T cells into patients, has elicited dramatic clinical responses in leukaemia patients recently. However, solid tumour remains a major challenge as tumour employs a number of strategies to prevent effector T cells reaching the tumour sites and attacking cancer by generating a highly immunosuppressive microenvironment. Current strategies are focused on controlling the immune system or the microenvironment using biochemical immunomodulatory reagents to enhance T cell based immunotherapy. Approaches exploiting biophysical and mechanical cues for immunomodulation are largely underappreciated. In this proposal, we aim to exploit mechanical immunoengineering strategies through biophysical cues to develop novel immune related treatments to enhance the efficacy and safety of adoptive T cell therapy for cancer. We will first develop a mechano-training approach to promote the T cell infiltration into tumour tissues using engineered microfluidic system for controlled force application on T cells in a high through-put manner. Second, we will develop a mechano-responsive nanoparticle delivery system to selectively deliver T-cell-supporting drugs in tumour to overcome the immune suppression in the microenvironment and enhance T cell functions for killing cancer. Third, we will develop mechano-inducible cytokine-secreting T cell therapies to augment the efficacy and minimize the toxicity of ACT by exploiting and targeting the difference in tissue stiffness between tumour and healthy tissues. This proposed project will open a new horizon for immunoengineering through biomechanical modulation of immunity for enhanced cancer immunotherapy and provide insight into the fundamentals of mechanotransduction in immune system in health and disease.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

ERC-STG - Starting Grant

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(si apre in una nuova finestra) ERC-2018-STG

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Istituzione ospitante

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Contributo netto dell'UE
€ 1 499 800,00
Indirizzo
BATIMENT CE 3316 STATION 1
1015 Lausanne
Svizzera
Regione
Schweiz/Suisse/Svizzera Région lémanique Vaud
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 499 800,00

Beneficiari (1)