T-cell receptor recognizing melanoma-associated antigen (TCR-MAA) (TCR-MAA)

The T-cell receptor (TCR) recognizing melanoma-associated antigen (MAA) peptides presented on Major Histocompatibility Complex (MHC) molecules is a pivotal therapeutic target in immuno-oncology, particularly for adoptive cell transfer and bispecific engagers. These TCRs are designed or selected to bind with high affinity to intracellular melanoma antigens—such as MART-1, gp100, MAGE-A4, or NY-ESO-1—that have been processed into short peptides and displayed by HLA molecules (typically HLA-A*02:01) on the tumor cell surface (Rosenberg et al., JCO 2011). Unlike CAR-T cells which are limited to surface proteins, TCR-based therapies can access the vast array of intracellular tumor-specific proteins, significantly expanding the targetable proteome in melanoma. Drugs targeting this system, such as the bispecific Tebentafusp or TCR-engineered T-cells like Afamitresgene autoleucel, work by bridging or redirecting T-cells to recognize and lyse these malignant cells (Nathan et al., NEJM 2021). However, the clinical application is challenged by the potential for on-target off-tumor toxicity, as some targeted antigens are also expressed in normal melanocytes found in the skin, uvea, and cochlea, leading to side effects like vitiligo or uveitis (Johnson et al., Blood 2009).

Other names

Melanoma-specific T-cell receptorMelanoma-associated antigen-specific T-cell receptorMART-1-specific TCRgp100-specific TCRMAGE-specific TCRTCR-T

T-cell receptor-mediated recognition of peptide-MHC complexes leading to T-cell activation and tumor cell lysis