Leukemia-associated antigen peptide-Major Histocompatibility Complex (LAA-MHC) (LAA-MHC)

Leukemia-associated antigen (LAA) peptides presented on Major Histocompatibility Complex (MHC) molecules are specialized targets for immunotherapy in Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia (ALL). These targets are formed when intracellular proteins—such as Wilms Tumor 1 (WT1), PRAME, or Proteinase 3—are degraded by the proteasome into short peptides and subsequently loaded onto MHC Class I or II molecules for surface display (PMID: 31534003). This mechanism allows the immune system to monitor the internal state of the cell, identifying malignant transformations that do not necessarily involve surface protein changes (PMID: 19096015). Therapeutic interventions, including peptide vaccines (e.g., Galinpepimut-S) and T-cell receptor (TCR)-engineered T-cells, are designed to recognize these specific peptide-HLA combinations to induce targeted cell lysis (PMID: 33613533). However, the efficacy of these treatments can be limited by HLA downregulation or the heterogeneity of antigen expression within the tumor population (PMID: 28637677).

Other names

Tumor-associated antigen (TAA) peptidespHLA complexesLeukemia-specific neoantigensMinor histocompatibility antigens (mHags)Leukemia-associated antigens (LAAs)

Induction of antigen-specific T-cell mediated cytotoxicity through the recognition of peptide-MHC complexes by T-cell receptors (TCRs) or TCR-like antibodies.