T-cell receptor recognizing the BCR-ABL b2a2 peptide–HLA complex (BCR-ABL b2a2 TCR)

The T-cell receptor (TCR) recognizing the BCR-ABL b2a2 peptide–HLA complex is a specialized immune receptor engineered to target the neoantigen produced by the Philadelphia chromosome translocation (t(9;22)). This translocation creates the BCR-ABL fusion protein, a constitutive tyrosine kinase that drives chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) (Blood, 2012). The b2a2 junction is a specific splice variant that generates a unique amino acid sequence at the fusion point, serving as a tumor-specific neoantigen (Leukemia, 1996). This TCR is designed to recognize the b2a2 junctional peptide when it is processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, such as HLA-A*03:01 or HLA-A*11:01. In clinical development, this TCR is utilized in adoptive cell transfer, specifically TCR-engineered T-cell (TCR-T) therapy, to redirect the patient's immune system against leukemic cells (Frontiers in Immunology, 2020). By binding to the peptide-HLA complex, the TCR triggers T-cell activation, leading to the release of cytotoxic granules and the selective destruction of Ph+ cells. This therapeutic approach aims to provide a curative option for patients who are resistant to standard tyrosine kinase inhibitors or those experiencing molecular relapse (Journal of Hematology & Oncology, 2021).

Other names

BCR-ABL b2a2-specific TCRb2a2 junction-specific T-cell receptorPhiladelphia chromosome-specific TCRBCR-ABL fusion peptide-specific TCR

Engineered T-cells expressing the TCR recognize the b2a2 fusion peptide presented by HLA molecules on leukemic cells, leading to T-cell activation and targeted lysis of the tumor cells (Blood, 2012).