Tyrosinase 368–376 peptide presented by HLA-A*02:01 (Tyr368-376/HLA-A*02:01)

The Tyrosinase 368–376 peptide presented by HLA-A*02:01 is a well-characterized tumor-associated antigen (TAA) complex primarily utilized in the development of immunotherapies for metastatic melanoma (Wolfel et al., 1994, Eur. J. Immunol.). Tyrosinase is a rate-limiting enzyme in melanin synthesis, and while it is overexpressed in melanoma, it is also present in normal melanocytes (Skipper et al., 1996, J. Exp. Med.). The specific epitope, often found in its deamidated form (YMDGTMSQV), is presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule. This complex is targeted by various therapeutic modalities, including T-cell receptor (TCR) engineered T-cells, peptide vaccines, and bispecific T-cell engagers such as ImmTACs (Immunocore, 2023). Because the target is a differentiation antigen, clinical use is associated with on-target, off-tumor toxicities affecting pigmented tissues in the skin, eyes, and ears. It remains a significant target for HLA-A*02:01-positive patients due to the high prevalence of tyrosinase expression in melanoma lesions.

Other names

YMDGTMSQVYMNGTMSQVTyrosinase peptide 368-376HLA-A2 restricted tyrosinase antigenTyrosinase(368-376)/HLA-A*02:01

T-cell receptor (TCR) binding and subsequent activation of cytotoxic T lymphocytes to induce tumor cell lysis.