T-cell receptor complex (TCR complex) recognizing melanoma-associated peptide-MHC (TCR)

The T-cell receptor (TCR) complex is a multi-subunit transmembrane assembly on T lymphocytes that recognizes specific antigenic peptides presented by Major Histocompatibility Complex (MHC) molecules (Janeway's Immunobiology). In melanoma, this complex is targeted by engineering TCRs to recognize melanoma-associated antigens (MAAs) like gp100, MART-1, and NY-ESO-1 (Robbins et al., 2011). Unlike CAR-T cells, TCR-based therapies can identify intracellular proteins that are processed and presented as peptides, broadening the range of targetable tumor markers. Therapeutic modalities include TCR-engineered T-cell (TCR-T) therapies and soluble bispecific TCR molecules, such as Tebentafusp, which redirects T-cells to attack tumor cells (Nathan et al., 2021). These treatments are highly specific and depend on the patient's HLA genotype, most commonly HLA-A*02:01. Clinical applications have shown success in metastatic and uveal melanoma, providing a novel approach for patients with limited options. However, the therapy carries risks such as cytokine release syndrome (CRS) and on-target, off-tumor toxicities in tissues expressing the target antigen, such as the skin or eyes. Monitoring for HLA expression and antigen density is crucial for patient selection and treatment efficacy.

Other names

Melanoma-specific T-cell receptorTCR-pMHC complexgp100-specific T-cell receptorNY-ESO-1-specific T-cell receptorMAGE-A4-specific T-cell receptorMART-1-specific T-cell receptor

T-cell redirection and activation via MHC-restricted recognition of melanoma-associated peptides.