T-cell receptor specific for tyrosinase peptide–HLA complex (TCR-tyrosinase/HLA)

T-cell receptors (TCRs) specific for tyrosinase peptide–HLA complexes are therapeutic targets used in the development of adoptive cell therapies and bispecific molecules for melanoma. Tyrosinase is a melanocyte-differentiation antigen essential for melanin production, and its expression is largely restricted to melanocytes and melanoma cells (PMID: 10449133). The most common target is the tyrosinase 369-377 peptide (YMDGTMSQV) presented by HLA-A*02:01. Therapeutic strategies involve engineering T cells to express high-affinity TCRs (TCR-T) or using soluble bispecific TCRs (ImmTACs) to bridge endogenous T cells to the tumor (PMID: 31461650). While these therapies show promise in treating metastatic melanoma, they can cause on-target off-tumor toxicities, such as vitiligo and uveitis, due to the presence of tyrosinase in normal melanocytes in the skin and eyes (PMID: 19380636). Clinical development of these agents, such as ADP-A2TYR and IMC-F10V, focuses on maximizing anti-tumor efficacy while managing these predictable autoimmune-like side effects.

Other names

Tyrosinase-specific T-cell receptorTyrosinase-reactive TCRHLA-A*02:01-restricted tyrosinase TCRTCR specific for tyrosinase 369-377

Adoptive T-cell therapy (TCR-T) or bispecific TCR-based engagers (ImmTACs) that redirect T-cell cytotoxicity toward cells presenting tyrosinase-derived peptides on HLA-A*02:01 molecules (PMID: 31461650).