Leukemia-associated antigen peptide–HLA complex (LAA-pHLA) (LAA-pHLA)

Leukemia-associated antigen (LAA) peptide–HLA complexes are molecular structures presented on the surface of leukemic cells, consisting of a short peptide fragment derived from intracellular proteins bound to a Human Leukocyte Antigen (HLA) molecule (Yao et al., 2024). These complexes are essential for the adaptive immune system, as they allow T-cells to monitor the internal proteome of a cell and identify malignant transformations that are not visible via traditional surface markers (Hofmann et al., 2021). In leukemia, these peptides often originate from overexpressed or mutated proteins such as Wilms tumor 1 (WT1), PRAME, or Proteinase 3, which play roles in cell proliferation and survival (Sellos-Moura et al., 2020). Therapeutic interventions targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, peptide-based vaccines, and TCR-like antibodies (TCRm) designed to bind the specific peptide-HLA interface with high affinity (Dao et al., 2013). These approaches enable the targeting of high-value intracellular oncogenic drivers, expanding the range of treatable targets beyond standard surface antigens like CD19 or CD20. However, clinical application is challenged by the requirement for specific HLA alleles in patients (HLA restriction) and the risk of immune escape through the downregulation of the antigen processing machinery or HLA expression. Additionally, the potential for off-target toxicity exists if the targeted peptide is presented on healthy tissues, necessitating rigorous screening of candidate antigens. Despite these challenges, LAA-pHLA complexes remain a cornerstone of next-generation immunotherapy for hematologic malignancies.

Other names

pHLA complexpMHC complexLeukemia-specific peptide-MHC complexTumor-associated antigen peptide-HLA complex

T-cell receptor (TCR) binding and activation, Induction of antigen-specific cytotoxic T-lymphocyte (CTL) response, Antibody-dependent cellular cytotoxicity (ADCC)