Characterization of TrkB autoantibodies reveals an agonist binding region in breast cancer

The neurotrophin receptor TrkB has been increasingly implicated in the progression, metastasis, and drug resistance of breast cancer. While its natural ligand, brain-derived neurotrophic factor (BDNF), activates TrkB signaling to promote tumor cell proliferation and survival. In this study, we identified that certain patient-derived antibodies can function similarly as agonists, we investigated their binding region and functional activities using a reporter cell assay and a combination of epitope mapping. Our results reveal distinct binding patterns associated with agonistic activity and identify a key activation site targeted by these antibodies. These findings suggest that TrkB agonist autoantibody mediated modulation of this region may influence cancer cell signaling and providing a potential basis for further investigation into immune-related mechanisms in breast cancer.