Construction and Functional Characterization of TCR-T Cells Targeting MAGE-C2

This study aimed to construct engineered TCR-T cells targeting the tumor antigen MC2 (MAGEC2), evaluate their specific anti-tumor activities in vitro and in vivo, and provide experimental evidence for adoptive immunotherapy of MC2-positive tumors. Specific TCRs recognizing MC2/HLA-A*02:01 were screened fromactivated human CD8⁺ T cells and identified by single-cell sequencing. The dominant TCR (W2) was screened andobtained, and after murineization modification, it was inserted into a lentiviral vector, and transduced into T cells. Tetramer staining was used to verify the expression level and antigen specificity of the TCR. Using MC2-expressing K562 cells and peptide-loaded T2 cells as target cells, cytokine secretion and cytotoxicity were detected in a coculture system. W2-TCR-T cells were adoptively transferred into NCG tumor-bearing nude mouse models to assesstheir in vivo tumor-suppressive efficacy. High-affinity W2-TCR-T cells with biological functions were successfullyobtained. These cells could specifically recognize matched target cells, promote the secretion of IFN-γ (interferon-γ)and TNF-α (tumor necrosis factor-α), and kill tumor cells in a dose-dependent manner. In vivo experiments showedthat W2-TCR-T cells significantly inhibited tumor growth, and the anti-tumor effect was enhanced with an increasein the infused cell dose. The optimized W2-TCR-T cells targeting MAGE-C2 exhibit favorable antigen recognitionability, can effectively eliminate antigen-positive tumor cells, and exert a remarkable in vivo anti-tumor effect, indicating promising application prospects.

CSTR: 32200.14.cjcb.2026.06.0001