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T-FITNESS: Toward empowering CAR-T therapies for solid tumors

September 1, 2022
The Genopole team SysFate, under the direction of Marco Mendoza, is participating in the international project T-FITNESS, launched 1 September 2022. The project, selected by the European Innovation Council, aims to resolve the difficulty of T-cell exhaustion in CAR-T therapies for solid tumors.
CAR-T Cells  - SysFate - T-FitnessFit CAR-T Cells  - SysFate - T-FitnessFit

Chimeric antigen receptor (CAR) T-cells “* are genetically modified T lymphocytes aimed particularly at the treatment of cancers. They have shown great promise, especially for blood malignancies, with, for example, remarkable results reported in acute lymphoblastic leukemia, the most frequent childhood leukemia, and in diffuse large B cell lymphoma, a mostly adulthood lymphoma. Conceptually, CAR-T cells should be equally applicable in solid-tumor cancers but results to date have been disappointing, due largely to a loss of efficacy of the CAR-T systems over time, called “T-cell exhaustion.”
The project T-FITNESS** seeks to resolve this problem of T-cell exhaustion via the use of synthetic microRNA-based circuits able to regulate the overexpression of certain key transcription factors identified as causative agents of it. T-FITNESS was selected by EIC Pathfinder, a European program whose objective is to support the development of disruptive innovations.
The identification of the transcription factors to be targeted is the first major step of T-FITNESS. Thereto, the project will benefit from TETRAMER, a computer application developed in-house by SysFate, under the direction of Marco Antonio MENDOZA-PARRA within the Genomics Metabolics unit (Genoscope – CEA / CNRS / University of Évry).

TETRAMER is capable of reconstructing gene regulation networks from transcriptomics data and identifying key transcription factors in the reconstructed networks through transcription regulation simulation methods.

The Genopole research team has validated TETRAMER in neuronal differentiation, cellular reprogramming and tumorigenic transformation in vitro. For the T-FITNESS project, the team will exploit transcriptomics data obtained from CAR-T systems.

The project T-FITNESS

T-FITNESS was launched on 1 September 2022 and will continue for four years. Its long-term objective is to develop a novel T-cell reprogramming technology enabling immunotherapies for all types of malignant tumors.

More information

* CAR-T cells

CAR-T cell therapy involves harvesting patient T lymphocytes and modifying them genetically to target tumor cells specifically. This modification makes the T lymphocytes express a particular protein called a chimeric antigen receptor (CAR). That receptor is what makes the modified T cells able to recognize antigens specific to the cells of the targeted tumor and set off a cytotoxic immune reaction against those tumor cells.


Fine-tuning T cell Networks of Exhaustion by Synthetic Sensors.
T-FITNESS is a four-year project coordinated by the Leibniz Institute for Immunotherapy. The project brings together a consortium of academic and industrial partners from five European countries who, together, provide a unique collection of competencies in T-cell immunology and therapeutics, genome editing, cGMP, bioinformatics and communication.

Article posted on 13 September 2022

With the support from
Région île de France