Tumor targeting through a TME-specific regulatory code and programmable CAR T cells

Informazioni relative al progetto

TRAP-CART

ID dell’accordo di sovvenzione: 101026676

DOI

10.3030/101026676

Progetto chiuso

Data della firma CE 31 Marzo 2021

Data di avvio 1 Aprile 2021

Data di completamento 31 Marzo 2023

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 174 167,04

Contributo UE

€ 174 167,04

Coordinato da

CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Austria

Periodic Reporting for period 1 - TRAP-CART (Tumor targeting through a TME-specific regulatory code and programmable CAR T cells)

Periodo di rendicontazione: 2021-04-01 al 2023-03-31

Sintesi del contesto e degli obiettivi generali del progetto

This project aimed at potentiate cancer immunotherapies by modifying cells of the immune system and improve current cell therapies based on CAR T cells.
The project is very important for society since cancer is one of the leading cause of death and suffering worldwide, and new strategies to improve cancer treatment are urgently needed.
The overall objectives of the project are to generate a publicly available database of sequences which could be exploited to render immunotherapies more cancer-specific and provide a proof-of-concept for our new strategy based on gene engineering.
During the action we were able to accumulate data concerning chromatin and epigenetic signatures of tumor associated macrophages (TAM) associated to enhancers specifically active in this context.
We have developed a strategy to set up the screening of these enhancers and promoters for their activity within the tumor. And we have developed ways to couple TAM engineering

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

From the beginning of the project we were able to characterize tumor associated macrophages (TAM) at the chormatin/epigenetc state, but also at the transcriptional level in our model of solid tumor. We also set up the basis to screen for enhancers and promoter active in TAM specifically using our model and generate a database of such enhancers and promoters specifically active inside the tumors.
We are generating CAR T cells able to respond to secreted external stimuli.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

This project will pave the way for new cancer immunotherapies that combines HSC-based TME engineering with programmable CAR T cells. More generally, it will allow to establish new ways to generate artificial and specific enhancers beyond the cancer field as well. We are committed to taking our results forward beyond the scope outlined above, toward tangible benefit for patients receiving existing CAR T cell therapies and for patients with cancers that constitute an unmet clinical need.

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