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

Informations projet

TRAP-CART

N° de convention de subvention: 101026676

DOI

10.3030/101026676

Projet clôturé

Date de signature de la CE 31 Mars 2021

Date de début 1 Avril 2021

Date de fin 31 Mars 2023

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 174 167,04

Contribution de l’UE

€ 174 167,04

Coordonné par

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)

Période du rapport: 2021-04-01 au 2023-03-31

Résumé du contexte et des objectifs généraux du projet

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

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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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