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

Project Information

TRAP-CART

Grant agreement ID: 101026676

DOI

10.3030/101026676

Project closed

EC signature date 31 March 2021

Start date 1 April 2021

End date 31 March 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 174 167,04

EU contribution

€ 174 167,04

Coordinated by

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)

Reporting period: 2021-04-01 to 2023-03-31

Summary of the context and overall objectives of the project

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

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.

mc-report-fp.png