BCR-ABL fusion protein junctional peptide-HLA complex (BCR-ABL/HLA)

The BCR-ABL fusion protein junctional peptide-HLA complex is a tumor-specific neoantigen arising from the Philadelphia chromosome translocation, t(9;22)(q34;q11), which is the hallmark of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (Ph+ ALL) [Source: National Cancer Institute]. This genetic rearrangement fuses the BCR and ABL1 genes, resulting in a chimeric protein with a unique amino acid sequence at the fusion junction that does not exist in normal cells [Source: UniProt]. These junctional proteins are processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, primarily Class I, where they can be recognized by the T-cell receptor (TCR) of cytotoxic T-lymphocytes [Source: PubMed PMID 10447413]. As a truly tumor-specific antigen, this complex is an ideal target for immunotherapies such as peptide-based vaccines and TCR-engineered T-cell therapies, aiming to eliminate leukemic cells while sparing healthy tissue [Source: ClinicalTrials.gov]. However, the effectiveness of targeting this complex is limited by HLA restriction, as specific peptides only bind to certain HLA alleles, and by the relatively low density of these complexes on the leukemic cell surface [Source: PubMed PMID 22431567]. Furthermore, the emergence of resistance through the downregulation of HLA or antigen processing machinery remains a significant therapeutic challenge [Source: PubMed PMID 15507661].

Other names

BCR-ABL neoantigenBCR-ABL junctional epitopePhiladelphia chromosome fusion peptideBCR-ABL p210 junctional peptideBCR-ABL p190 junctional peptide

Induction of a targeted cytotoxic T-lymphocyte (CTL) response against cells presenting the unique BCR-ABL fusion neoepitope on HLA molecules.