Preferentially expressed antigen in melanoma-derived peptide–MHC class I complex (PRAME-peptide-MHC complex)

The Preferentially Expressed Antigen in Melanoma (PRAME)-derived peptide–MHC class I complex is a highly specific tumor target formed by the presentation of intracellular PRAME fragments on the cell surface. PRAME is a cancer-testis antigen that is typically expressed in immune-privileged sites like the testis but is aberrantly overexpressed in a wide range of cancers, including melanoma, lung cancer, and various leukemias (Source: nih.gov, immatics.com). Because PRAME is an intracellular protein, it is inaccessible to traditional monoclonal antibodies; however, its degradation into peptides and subsequent presentation by Major Histocompatibility Complex (MHC) Class I molecules (most commonly HLA-A*02:01) creates a targetable surface epitope (Source: acir.org, tandfonline.com). Therapeutic interventions such as T-cell receptor (TCR)-engineered T cells and bispecific T-cell engagers are designed to recognize these specific peptide-MHC complexes with high affinity (Source: patsnap.com, onclive.com). Upon binding, these therapies recruit and activate T cells to induce direct cytotoxic killing of the tumor cells. This targeting strategy effectively expands the reach of immunotherapy to include intracellular oncogenic drivers, offering a promising approach for treating solid and hematological malignancies with limited off-tumor toxicity (Source: ashpublications.org, mdpi.com).

Other names

PRAME-HLA complexPRAME-MHC complexHLA-A*02:01/PRAME peptide complexALYVDSLFFL/HLA-A*02:01 complexSLLQHLIGL/HLA-A*02:01 complexPRAME425-433/HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes, Bispecific T-cell engagement (recruiting CD3+ T cells to the MHC complex), and TCR-mimic (TCRm) antibody-mediated targeting.