Exploring high-affinity MAGE-A3-specific T-cell receptors derived from healthy donor PBMCs: A preclinical evaluation

Authors: Xueying Wua, Peiying Wangc, Ning Shenc, Kaitao Jiangc, Jinyue Yic, Qianli Zhaoc, Shuaibing Renc, Ying Hanc, Junhang Zhangc, Lu Qianc, Henghui Zhanga, and Hui Zeng

Translational Research, 25 February 2026

Researchers use the Maestro Z platform to demonstrate potent, antigen-specific cytotoxicity of a candidate TCR against MAGE-A3–expressing tumor cells. 

In this study, researchers developed a novel approach to identify tumor antigen–specific T-cell receptors (TCRs) from healthy donor PBMCs, addressing a major bottleneck in advancing TCR-based immunotherapies. Focusing on the cancer-testis antigen MAGE-A3, the team screened multiple candidate sequences and identified G0507 as a promising lead for clinical development due to its high sensitivity and specificity.  

Using Axion BioSystems’ Maestro Z platform for label-free impedance-based cytotoxicity assays, the researchers evaluated the functional activity of G0507 TCR-T cells in real time. G0507 demonstrated strong and selective killing of tumor cells expressing HLA-A*02:01 and/or MAGE-A3, including both engineered and naturally expressing cell lines. Cytotoxicity increased further when target cells presented higher levels of the MAGE-A3 peptide, while no enhanced killing was observed against cells with unrelated peptides—highlighting the receptor’s antigen specificity.  

Together, these findings underscore the importance of epitope presentation in driving TCR efficacy and position G0507 as a compelling candidate for further development. More broadly, the study demonstrates how combining novel TCR discovery approaches with functional, real-time cytotoxicity assays can accelerate the translation of targeted immunotherapies