T-cell receptor recognizing EWS-FLI1-derived peptide epitopes (EWS-FLI1 TCR)

The T-cell receptor (TCR) recognizing EWS-FLI1-derived peptide epitopes is a specialized immune receptor used in adoptive T-cell therapy to target Ewing sarcoma. Ewing sarcoma is characterized by a specific chromosomal translocation, most commonly t(11;22)(q24;q12), which creates the EWS-FLI1 fusion protein. Because this fusion protein is unique to tumor cells and acts as a neoantigen, it serves as an ideal target for immunotherapy. The TCR is engineered to recognize specific fragments of this fusion protein when they are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, typically HLA-A*02:01. In a therapeutic context, a patient's own T-cells are modified ex vivo to express this specific TCR and then re-infused into the patient. Once inside the body, these engineered T-cells identify and bind to the EWS-FLI1 peptide-MHC complexes on the surface of sarcoma cells, triggering a cytotoxic immune response that leads to tumor cell death. This approach bypasses the need for surface-expressed proteins, allowing the immune system to target intracellular oncogenic drivers. Clinical development focuses on optimizing TCR affinity and ensuring high specificity to avoid cross-reactivity with normal tissues.

Other names

EWS-FLI1-specific T-cell receptorEwing sarcoma breakpoint region 1-Friend leukemia virus integration 1 transcription factor-specific T-cell receptorEWS-FLI1 neoantigen-specific TCR

Adoptive cell transfer of T-cells engineered to express a specific T-cell receptor (TCR) that recognizes EWS-FLI1 fusion protein-derived peptides presented by Major Histocompatibility Complex (MHC) molecules, leading to targeted destruction of Ewing sarcoma cells.