Leukemia-associated antigen peptide-HLA class I complex (LAA-pHLA)

Leukemia-associated antigen (LAA) peptide-HLA class I complexes are specialized molecular targets formed when intracellular proteins overexpressed in leukemic cells are processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules. These complexes allow the immune system to monitor the internal proteome of malignant hematopoietic cells, identifying proteins like Wilms Tumor 1 (WT1), PRAME, and Proteinase 3 that are not typically found on the cell surface (Source: Anguille et al., 2012, PubMed). By targeting these specific peptide-MHC combinations, therapies such as TCR-engineered T-cells (TCR-T), peptide vaccines, and TCR-like bispecific molecules can selectively induce apoptosis in leukemia cells while sparing most healthy tissues (Source: Lichtenegger et al., 2017, Frontiers in Oncology). This approach is particularly valuable in hematological malignancies where traditional surface markers may be shared with healthy hematopoietic stem cells. However, the success of these therapies is highly dependent on the patient's HLA haplotype and the stability of antigen presentation, as tumors often attempt to evade detection by downregulating HLA expression (Source: NIH, National Cancer Institute). Clinical development focuses on identifying highly specific peptides that minimize the risk of autoimmune cross-reactivity with essential healthy organs.

Other names

Leukemia-associated antigensHLA-restricted leukemia-associated peptidesMHC class I-restricted leukemia antigensLeukemia immunopeptidome targetsMinor histocompatibility antigens (mHags)Tumor-associated antigen (TAA) peptides

Recognition of the specific peptide-HLA complex by endogenous or engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to the formation of an immunological synapse and subsequent T-cell mediated lysis (perforin/granzyme release) of the malignant hematopoietic cell.