L Antigen Family Member 1A (LAGE-1A) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) (LAGE-1A/HLA-A*02:01)

The LAGE-1A-derived peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for advanced cancer immunotherapies. The peptide, most commonly the 9-mer SLLMWITQC (residues 157-165), is derived from the L Antigen Family Member 1A (LAGE-1A), also known as CTAG2 (UniProt P78358, NIH Tetramer Core Facility). This protein belongs to the cancer-testis antigen (CTA) family, which is characterized by high expression in various malignancies—such as synovial sarcoma, melanoma, and non-small cell lung cancer—but restricted expression in normal adult tissues, primarily the immune-privileged testis (PubMed, NIH). When presented on the cell surface by the Human Leukocyte Antigen A*02:01 (HLA-A*02:01) molecule, this complex can be recognized by specific T-cell receptors (TCRs) (Frontiers in Immunology). Therapeutic interventions, including TCR-engineered T-cell (TCR-T) therapies like letetresgene autoleucel and bispecific T-cell engagers (ImmTACs), are designed to bind this pMHC complex with high affinity to induce a targeted cytotoxic immune response against tumor cells (AACR Journals, ResearchGate). Clinical trials have demonstrated the potential of targeting this complex to achieve durable responses in patients with solid tumors, although challenges such as cytokine release syndrome and potential off-target cross-reactivity with similar peptides in the human proteome must be carefully managed (Science Translational Medicine, Frontiers in Immunology).

Other names

NY-ESO-1/LAGE-1a shared epitopeSLLMWITQC-HLA-A*02:01 complexCTAG2-derived peptide-HLA-A*02:01 complexLAGE-1A-derived peptide presented by HLA-A*02:01

Engineered T-cell receptor (TCR) therapy and bispecific T-cell engagers (ImmTACs) that specifically recognize the peptide-MHC complex to trigger T-cell mediated lysis of tumor cells.