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Melanoma-associated antigen 10 (MAGE-A10) is a member of the cancer-testis antigen (CTA) family, characterized by restricted expression in immune-privileged germ cells and aberrant overexpression in various malignancies, including non-small cell lung cancer and melanoma [1.1.1, 1.5.1]. The specific 9-mer peptide GLYDGMEHL (residues 254-262) is processed and presented on the tumor cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule [1.3.2, 1.4.2]. This peptide-MHC (pMHC) complex serves as a highly specific target for adoptive T-cell therapies, most notably Specific Peptide Enhanced Affinity Receptor (SPEAR) T-cells like ADP-A2M10 [1.2.3, 1.2.5]. By engineering T-cells to express high-affinity T-cell receptors (TCRs) specific to this pMHC, the immune system can be directed to selectively recognize and eliminate MAGE-A10-positive tumor cells [1.1.1, 1.4.4]. Clinical development of MAGE-A10-targeted therapies has demonstrated an acceptable safety profile, although programs were often transitioned to MAGE-A4 due to overlapping expression patterns and superior clinical responses in the latter [1.2.2, 1.2.4].
T-cell receptor (TCR) binding and activation of engineered T-cells leading to tumor cell lysis.
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