T cell receptor specific for HLA-A2-restricted melanoma-associated antigens (TCR (HLA-A2/Melanoma Antigens))

The T cell receptor (TCR) specific for HLA-A2-restricted melanoma-associated antigens is a specialized immune receptor engineered or selected to recognize peptide fragments from proteins like MART-1, gp100, and Tyrosinase. These proteins are melanocyte differentiation antigens that are highly overexpressed in melanoma cells but also present in normal melanocytes. The TCR recognizes these peptides only when they are presented by the specific Major Histocompatibility Complex (MHC) allele HLA-A*02:01, making the therapy restricted to patients with this genetic background (Citations: PubMed: 11207388, PubMed: 21670458). In a therapeutic context, these TCRs are used in TCR-engineered T cell (TCR-T) therapies or as part of bispecific molecules like Tebentafusp, which targets gp100 to treat uveal melanoma (Citations: NEJM: 385:1196-1206). Upon binding to the peptide-HLA complex on the tumor surface, the TCR triggers the release of cytotoxic granules and cytokines, leading to tumor cell lysis. However, because these antigens are also expressed in the skin, eyes, and inner ear, treatment can lead to 'on-target, off-tumor' toxicities such as vitiligo, uveitis, and ototoxicity (Citations: J Clin Oncol: 27(32):5414-5420).

Other names

MART-1-specific T cell receptorgp100-specific T cell receptorTyrosinase-specific T cell receptorMelan-A-specific T cell receptorHLA-A*02:01 restricted TCRMelanocyte differentiation antigen-specific TCR

Adoptive T-cell therapy (TCR-T) and bispecific T-cell engagers (ImmTACs) utilize these TCRs to redirect T cells to recognize and kill tumor cells presenting specific melanoma-associated peptides (MART-1, gp100, or Tyrosinase) on HLA-A2 molecules.