Melanoma-associated antigen C2-specific T-cell receptor (MAGE-C2 TCR)

MAGE-C2-specific T-cell receptors (TCRs) are specialized immune receptors engineered to recognize specific peptide fragments of the Melanoma-associated antigen C2 (MAGE-C2) presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02 [Immatics, 2023]. MAGE-C2, also known as Cancer/Testis Antigen 10 (CT10), is a highly immunogenic protein that is frequently overexpressed in various cancers, such as melanoma, hepatocellular carcinoma, and non-small cell lung cancer, while remaining silent in normal adult tissues except for the immune-privileged testis [UniProt, 2024; PMID: 10449774]. These TCRs are the core component of TCR-engineered T-cell (TCR-T) therapies, where they redirect the patient's immune system to specifically target and destroy MAGE-C2-positive malignant cells [PMID: 33028634]. Upon binding to the MAGE-C2 peptide-MHC complex, the TCR initiates a signaling cascade that leads to T-cell activation, the secretion of pro-inflammatory cytokines like IFN-gamma, and the direct lysis of tumor cells via the perforin/granzyme pathway [PMID: 21148345]. Therapeutic candidates like IMA204 utilize high-affinity TCRs to maximize anti-tumor efficacy while minimizing off-target risks [Immatics, 2024]. However, the development of these receptors faces challenges such as potential cross-reactivity with similar peptides in healthy tissues and the requirement for specific HLA genotypes in patients [PMID: 28671620].

Other names

CT10-specific T-cell receptorMAGE-C2-specific TCRMAGE-C2/MHC-targeting TCRMAGE-C2-specific T-cell receptors recognizing MAGE-C2-derived peptide–MHC complexes

Engineered T-cell receptors bind specifically to MAGE-C2 peptide-MHC complexes on the surface of tumor cells, triggering T-cell activation, cytokine release, and direct lysis of the malignant cells [PMID: 33028634].