Episode 71: MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial
About this episode
This episode discusses a phase 1 trial of a bispecific T cell engager targeting MAGE-A4 and MAGE-A8 in solid tumors.
**Monday Immune Engager** — our weekly pick from the latest immune-engager digest. **Paper:** [MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial](https://doi.org/10.1038/s41591-026-04455-x) **Authors:** Martin Wermke, Sebastian Ochsenreither, Dirk Jaeger, Heiko Becker, et al. **Journal:** Nature Medicine, 2025 **Why it matters:** By using an engineered T cell receptor domain instead of an antibody to target intracellular cancer-testis antigens presented on the cell surface via HLA, IMA401 opens a route to solid tumor immunotherapy that sidesteps the target-scarcity problem that has long limited bispecific T cell engagers in this setting. --- **Summary** Conventional bispecific T cell engagers (TCEs) are constrained to surface antigens, which are rarely tumor-specific enough in solid tumors to avoid on-target, off-tumor toxicity. IMA401 addresses this by replacing the antibody-based targeting arm with a high-affinity TCR domain that recognizes a peptide derived from the cancer-testis antigens MAGE-A4 and MAGE-A8 presented on the HLA-A\*02:01 allele — proteins that are epigenetically silenced in normal adult…
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