Melanoma-associated antigen 3-specific T-cell receptor (MAGE-A3-specific TCR) (MAGE-A3 TCR)

The Melanoma-associated antigen 3-specific T-cell receptor (MAGE-A3 TCR) is a specialized immune receptor engineered for use in adoptive T-cell therapy to treat various solid tumors. It specifically recognizes a peptide fragment of the MAGE-A3 protein, a member of the cancer-testis antigen family, when it is presented on the cell surface by the Human Leukocyte Antigen (HLA)-DP4 complex [1]. MAGE-A3 is an ideal therapeutic target because it is highly expressed in cancers such as melanoma, non-small cell lung cancer, and urothelial carcinoma, while remaining largely absent in healthy adult tissues except for the testis and placenta [2]. This TCR is typically transduced into a patient's own T cells, which are then expanded and re-infused to mount a targeted attack against the tumor. Unlike many TCRs that are restricted to MHC Class I (such as HLA-A2), this receptor is restricted to MHC Class II (HLA-DP4), which is highly prevalent in the Caucasian population and allows for the recruitment of a robust immune response involving both CD4+ and CD8+ T cells [3]. Clinical development of this target has been significantly influenced by the need to manage off-target effects, particularly a known risk of cross-reactivity with MAGE-A12 expressed in the central nervous system, which led to severe neurotoxicity in early trials [1]. [1] Morgan RA, et al. (2013) J Clin Oncol. [2] Kite Pharma/Gilead (2021) Pipeline Data. [3] Yao X, et al. (2016) Cancer Immunol Res.

Other names

Anti-MAGE-A3 TCRHLA-DP4-restricted MAGE-A3 T-cell receptorMAGE-A3:243-258-specific TCRMAGE-A3-specific T-cell receptor recognizing HLA-DP4/MAGE-A3 complex

The engineered T-cell receptor specifically binds to the MAGE-A3 peptide (residues 243-258) presented by the MHC Class II molecule HLA-DPB1*04:01 or *04:02 on the surface of tumor cells, triggering T-cell activation, cytokine production, and direct cytotoxic lysis of the target cell [1, 3].