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

Leukemia-associated antigenic peptides presented on HLA class I and II molecules represent a specialized class of therapeutic targets in immuno-oncology. These targets consist of short peptide fragments derived from intracellular proteins—such as Wilms' Tumor 1 (WT1), PRAME, or Proteinase 3—that are processed and displayed on the leukemia cell surface by the Major Histocompatibility Complex (MHC) (Source: Lichtenegger et al., 2019, Frontiers in Oncology). Unlike traditional surface antigens, these peptide-HLA (pHLA) complexes allow the immune system to detect internal oncogenic drivers and mutations, providing a broader range of targets for T-cell recognition (Source: Anguille et al., 2012, Vaccines). Therapeutic strategies targeting these complexes include peptide-based vaccines, T-cell receptor (TCR) engineered T-cells, and TCR-mimetic bispecific antibodies designed to trigger potent cytotoxic immune responses (Source: Van Driessche et al., 2005, Leukemia). While highly specific, these therapies are restricted by the patient's specific HLA genotype, most commonly targeting HLA-A*02:01, and face challenges such as tumor-mediated HLA downregulation (Source: SELLAS Life Sciences; ClinicalTrials.gov).

Other names

Leukemia-associated antigensLAAMHC-restricted leukemia antigensTumor-associated antigens in leukemiaMinor histocompatibility antigenspHLA complexes

Recognition of specific peptide fragments derived from leukemia-associated proteins (e.g., WT1, PRAME) presented by HLA molecules on the cell surface by T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to targeted T-cell mediated lysis of the malignant cells.