HLA-A*02:01-Melanoma antigen recognized by T cells 1 (26-35, 27L) complex (HLA-A*02:01/MART-1(27L))

The HLA-A*02:01-Melanoma antigen recognized by T cells 1 (26-35, 27L) complex is a specific peptide-major histocompatibility complex (pMHC) class I molecule that serves as a critical target in cancer immunotherapy, particularly for melanoma (PMID: 9430495). It consists of the HLA-A*02:01 allele presenting a modified decamer peptide (ELAGIGILTV) derived from the MART-1 (Melanoma Antigen Recognized by T cells 1) protein, also known as Melan-A (UniProt Q16655). The native peptide sequence is modified at position 27 from Alanine to Leucine (27L) to enhance its binding affinity to the HLA-A*02:01 molecule, thereby increasing the stability of the complex and its visibility to the immune system (PMID: 10359806). This complex is primarily expressed on the surface of melanoma cells and normal melanocytes, making it a focal point for T-cell receptor (TCR)-based therapies, including TCR-engineered T cells (TCR-T) like KITE-718 and bispecific TCR molecules like IMC-F10V (NCT03566147). Drugs targeting this complex work by redirecting cytotoxic T lymphocytes to recognize and eliminate cells displaying the MART-1 antigen. However, because MART-1 is also expressed in healthy melanocytes, therapeutic interventions carry risks of on-target, off-tumor toxicities affecting the skin, eyes, and ears, such as vitiligo and uveitis (PMID: 19228931). Monitoring for cytokine release syndrome and neurotoxicity is also essential during treatment with these potent immune-activating agents.

Other names

HLA-A*02:01/Melan-A (26-35) L27HLA-A2/MART-1 peptide complexELAGIGILTV-HLA-A*02:01MART-1 27L peptide-MHC complexHLA-A*02:01 presenting Melanoma antigen recognized by T cells 1

T-cell receptor (TCR) binding and T-cell redirection