T-cell receptor specific for BCR-ABL fusion protein (BCR-ABL TCR)

The T-cell receptor (TCR) specific for the BCR-ABL fusion protein is a specialized immune receptor that recognizes the unique neoantigen created by the Philadelphia chromosome translocation (t(9;22)). This translocation results in the BCR-ABL1 fusion gene, which encodes a chimeric protein (p210 or p190) characteristic of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL) (PMID: 25349174). CD8+ and CD4+ T cells expressing these TCRs can identify junctional peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of leukemic cells. This recognition triggers a cascade of immune activities, including the release of perforins and granzymes for direct cell lysis and the secretion of cytokines like IFN-gamma to orchestrate a broader anti-tumor response (PMID: 10448105). In clinical development, these TCRs are utilized in adoptive cell transfer (TCR-T therapy), where a patient's T cells are genetically modified to express the BCR-ABL-specific receptor to target TKI-resistant leukemia (PMID: 33619315). Because the BCR-ABL junction is a true neoantigen absent in normal tissues, these TCRs represent a highly specific therapeutic target with a favorable safety profile regarding off-target effects.

Other names

BCR-ABL-specific T-cell receptorp210-specific TCRp190-specific TCRPhiladelphia chromosome-specific TCRBCR-ABL-reactive TCR

The TCR recognizes specific peptide fragments derived from the BCR-ABL fusion junction presented by Major Histocompatibility Complex (MHC) molecules, leading to the activation of T cells and subsequent lysis of Philadelphia chromosome-positive (Ph+) leukemic cells (PMID: 10448105, PMID: 25349174).