Preferentially expressed Antigen in Melanoma (PRAME) peptide presented by Human Leukocyte Antigen A2 (HLA-A2) (PRAME/HLA-A2)

The PRAME peptide presented by HLA-A2 is a therapeutic target consisting of a specific epitope derived from the Preferentially expressed Antigen in Melanoma (PRAME) protein bound to the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule (Immatics, 2024; NIH, 2017). PRAME is a cancer-testis antigen that is highly expressed in various cancers—such as melanoma, non-small cell lung cancer, and acute myeloid leukemia—but has restricted expression in normal tissues, primarily the testes and ovaries (Wikipedia; NIH, 2023). Because PRAME is an intracellular protein, it is not accessible to traditional monoclonal antibodies; however, its degradation into peptides and subsequent presentation on the cell surface via MHC Class I molecules like HLA-A2 allows it to be targeted by T-cell-based therapies (OncLive, 2024; JCI, 2017). Current drug development efforts focus on T-cell receptor (TCR) engineered T-cell therapies (TCR-T) and bispecific T-cell engagers (such as ImmTACs) that recognize this specific peptide-MHC complex to induce potent, tumor-specific immune responses (Immunocore, 2023; Immatics, 2025). Clinical trials have demonstrated the potential of this target to treat a broad range of solid and hematological tumors in patients who are HLA-A*02:01 positive (ASCO, 2024; NIH, 2025). Therapeutic challenges include managing cytokine release syndrome and ensuring specificity to avoid on-target off-tumor effects in tissues with low-level PRAME expression (Immatics, 2025; Fred Hutch, 2024).

Other names

PRAME-HLA-A*02:01PRAME/A2PRAME-A02PRAME peptide-MHC complexPreferentially expressed antigen in melanoma peptide-HLA-A*02:01 complex

T-cell redirection and T-cell receptor-mediated cytotoxicity