T-cell receptor recognizing melanoma-associated peptide–MHC complexes (TCR-pMHC) (TCR-pMHC)

The T-cell receptor recognizing melanoma-associated peptide–MHC complexes is a specialized immune receptor used in advanced immunotherapies to target intracellular melanoma antigens. These receptors are engineered to recognize specific peptides, such as those from gp100, MART-1, or MAGE-A4, presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01 (Nathan et al., 2021). In TCR-T cell therapy, a patient's T cells are modified to express these high-affinity receptors, enabling them to identify and destroy tumor cells that present the target antigen (Johnson et al., 2009). Alternatively, soluble bispecific molecules like Tebentafusp use a TCR domain to bridge T cells to melanoma cells, triggering a potent immune response (FDA, 2022). This approach is particularly valuable for targeting internal proteins that are inaccessible to conventional antibody-based drugs. However, because some target antigens are also present in healthy melanocytes, treatment can lead to on-target, off-tumor toxicities affecting the skin, eyes, and ears (Robbins et al., 2011). Additionally, the requirement for a specific HLA genotype limits the eligible patient population for these therapies.

Other names

Melanoma-specific T-cell receptorMART-1-specific T-cell receptorgp100-specific T-cell receptorMAGE-A4-specific T-cell receptorNY-ESO-1-specific T-cell receptorTCR-T

TCR-mediated T-cell redirection and activation against peptide-MHC complexes