CAR T ceLls with Anti-exhaUstion Device for Immunotherapy Advancement

Descrizione del progetto

Immunoterapia con cellule CAR-T di nuova generazione per il cancro alle ovaie

L’immunoterapia offre un nuovo modo di combattere il cancro, sfruttando il sistema immunitario dell’organismo per riconoscere e distruggere le cellule tumorali. La terapia con cellule CAR-T, una forma di immunoterapia, consiste nel modificare geneticamente le cellule T del paziente stesso affinché esprimano recettori antigenici chimerici che bersagliano specifici marcatori tumorali. Nonostante le loro potenzialità, l’efficacia clinica delle cellule CAR-T nei tumori solidi rimane limitata, in parte a causa dell’esaurimento dei linfociti T all’interno del microambiente tumorale immunosoppressivo. Il progetto CLAUDIA, finanziato dal CER, si propone di superare questa barriera nel cancro ovarico sviluppando cellule CAR-T di nuova generazione progettate specificamente per resistere all’esaurimento. Queste cellule saranno dotate di interruttori molecolari programmabili che, contemporaneamente, riorganizzeranno la struttura interna della cellula e disattiveranno i meccanismi di difesa del tumore.

Obiettivo

Ovarian cancer (OC) is the 8th most commonly occurring cancer in women and it is estimated that by 2050 the number of women diagnosed with OC will rise over 55%. The main treatment modalities for OC, surgical resection and first-line chemotherapy, often fail the complete remission. CAR T cell-immunotherapy approved for the treatment of blood tumours have limited impact on solid tumors, including OC.
CLAUDIA develops next-generation anti-exhaustion HER2 CAR T cells (ex-CAR T) to overcome one of the key barriers in OC immunotherapy: T-cell exhaustion. Building on ERC Starting Grant results, CLAUDIA brings to in vivo preclinical models CAR T cells engineered with synthetic sensor-actuator circuits, that are activated by early exhaustion hallmarks and trigger local multi-therapeutic payloads combining (i) intracellular reprogramming to downregulate exhaustion-associated genes, and (ii) extracellular checkpoint interference to remodel the tumor microenvironment (TME).
This high-risk/high-gain Proof of Concept moves beyond basic research by demonstrating improved persistence and anti-tumor efficacy in an in vivo HER2+ OC xenograft model.
If successful, CLAUDIA will deliver a tumor-conditioned, autoregulated intervention expected to enhance CAR T durability, reduce systemic toxicity, and generalize across multiple solid tumors.
The exploitation strategy integrates two complementary routes, (i) Product Model → creation of an EU-based startup to develop ex-CAR T for OC, leveraging early partnerships with clinical distributors and manufacturing facilities; (ii) Technology Model → licensing CLAUDIA’s anti-exhaustion circuits to biotech and pharma leaders (e.g. Novartis, Gilead/Kite, Miltenyi).
Supported by IIT’s Technology Transfer Office for IP management, startup creation, and early regulatory planning, CLAUDIA aims to establish a new foundation in CAR T therapies for solid tumors, addressing urgent clinical needs and delivering significant societal impact.