Summary
"Cell-based immunotherapy, particularly adoptive cell transfer (ACT) using engineered T cells, holds great promise as a therapeutic strategy for cancer treatment. However, challenges such as the manufacturing process, excessive antigen exposure, and the hostile tumor microenvironment often lead to dysfunctional T cell products, limiting their effectiveness in treating both blood cancers and solid tumors. We propose a novel tool to define in vitro conditions to enhance T cell product fitness through the development of a synthetic reporter system for detecting T cell dysfunction states, referred to as SynT. This innovative system will incorporate a dual synthetic locus control region (sLCR) reporter, with one sLCR reporter indicating T cells in a potent ""serial killer"" mode and another sLCR reporter representing T cell dysfunction. By using SynT, we aim to screen for external signaling and pharmacological modulators that can enrich and reverse the dysfunctional state in CAR T cells. we will generate and validate a synthetic reporter of CAR T cell products function and dysfunction, and produce a media supplement that promotes ACT products functions.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101158338 |
| Start date: | 01-03-2024 |
| End date: | 31-08-2025 |
| Total budget - Public funding: | - 150 000,00 Euro |
Cordis data
Original description
"Cell-based immunotherapy, particularly adoptive cell transfer (ACT) using engineered T cells, holds great promise as a therapeutic strategy for cancer treatment. However, challenges such as the manufacturing process, excessive antigen exposure, and the hostile tumor microenvironment often lead to dysfunctional T cell products, limiting their effectiveness in treating both blood cancers and solid tumors. We propose a novel tool to define in vitro conditions to enhance T cell product fitness through the development of a synthetic reporter system for detecting T cell dysfunction states, referred to as SynT. This innovative system will incorporate a dual synthetic locus control region (sLCR) reporter, with one sLCR reporter indicating T cells in a potent ""serial killer"" mode and another sLCR reporter representing T cell dysfunction. By using SynT, we aim to screen for external signaling and pharmacological modulators that can enrich and reverse the dysfunctional state in CAR T cells. we will generate and validate a synthetic reporter of CAR T cell products function and dysfunction, and produce a media supplement that promotes ACT products functions."
Status
SIGNEDCall topic
ERC-2023-POCUpdate Date
12-03-2024
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