Generation, validation and use of a synthetic reporter of CAR T cell products fu...
Generation, validation and use of a synthetic reporter of CAR T cell products function and dysfunction
"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 an...
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Información proyecto SynT
Duración del proyecto: 18 meses
Fecha Inicio: 2024-02-05
Fecha Fin: 2025-08-31
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
"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.
"