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Targeted Immunocytokines by CaGing and local Release

Descrizione del progetto

Attivatore immunitario innato ingabbiato in modelli preclinici di cancro

Le terapie immunitarie hanno rivoluzionato il trattamento del melanoma e della leucemia, ma non si sono rivelate efficaci per tutti i tumori a causa della presenza di tipi di cellule immunitarie soppressive nei tumori. Sono stati sviluppati attivatori immunitari innati chimicamente bloccati che possono essere riattivati localmente, offrendo un’opzione potenzialmente sicura e potente. Il progetto TIGER, finanziato dal CER, valuterà l’efficacia del primo attivatore immunitario innato ingabbiato in un modello preclinico di tumore, verificandone la potenza, la farmacocinetica e il comportamento di aggressione/decadimento. Il progetto amplierà la gamma di attivatori innati, anticorpi e sostanze chimiche di uncaging utilizzabili. Inoltre, condurrà ricerche di mercato per identificare la migliore combinazione di attivatore tumorale-anticorpo immunitario per un ulteriore sviluppo clinico.

Obiettivo

Immune therapies have caused a paradigm shift in the treatment of melanoma and leukemias. However, the broad Immune therapies have caused a paradigm shift in the treatment of melanoma and leukemias. However, the broad application of these immune therapies to all cancers has not worked. One of the major reason for this failure is the presence of innate immune suppressive cell types in many tumour types, such as macrophages, NK-, dendritic, and myeloid cells. Tumour selective reactivation of these cells is considered one of the holy grails for the future of immune therapy.

Most endeavours in achieving this are severely hampered by the toxicity of innate immune activators: they cause strong off-site-on-target systemic immune activation, which can lead sepsis-like symptoms and death. Developing innate immune activating therapies that are both powerful and safe are therefore key to applying immune therapies across the cancer landscape.

As part of my ERC-CoG-Grant I have developed innnate immune activators that are chemically blocked, but that can be reactivated locally to offer. This approach can potentially serve as exactly the safe and potent innate activator required. By targeting the innate activators to the tumour and only activating them once they have accumulated there, we can decouple the therapeutic activity from the systemic toxicity that plagues these approaches.

In this proposal, we aim to evaluate the first such a caged innate immune activator in a pre-clinical cancer model. We will validate its potency, pharmacokinetics and caging/decaging behaviour. In addition, we will broaden the scope of the innate activators, antibodies and uncaging chemistries that can be applied. We will also perform market research to determine the optimal tumour-immune activator-antibody combination to take forward into clinical development and begin to take the necessary steps to spin out a company based on this work to bring these non-toxic innate activators to the clinic.

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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Istituzione ospitante

UNIVERSITEIT LEIDEN
Contribution nette de l'UE
€ 150 000,00
Indirizzo
RAPENBURG 70
2311 EZ Leiden
Paesi Bassi

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Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)