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

Rabia Parveen1, Srimathi Venkataraman2, Yu-Chieh Hsu3

  • 1International Master Program of Biomedical Sciences, China Medical University Taichung 406040, Taiwan.

American Journal of Cancer Research
|October 20, 2025
PubMed

Insights

Certain patient antibodies act as agonists for the neurotrophin receptor TrkB, influencing breast cancer progression. This research identifies key binding sites for these antibodies, suggesting new immune-related therapeutic avenues.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The neurotrophin receptor TrkB plays a role in breast cancer progression, metastasis, and drug resistance.
  • Brain-derived neurotrophic factor (BDNF) is a natural ligand that activates TrkB signaling, promoting tumor cell proliferation and survival.

Purpose of the Study:

  • To investigate if patient-derived antibodies can act as agonists for TrkB.
  • To identify the binding regions and functional activities of these agonistic antibodies.
  • To explore the potential of TrkB agonist autoantibodies in breast cancer immune-related mechanisms.

Main Methods:

  • Utilized reporter cell assays to evaluate functional activities.
  • Employed epitope mapping to determine antibody binding regions.
  • Analyzed distinct binding patterns associated with agonistic activity.

Main Results:

  • Identified specific patient-derived antibodies functioning as TrkB agonists.
  • Revealed distinct binding patterns correlating with agonistic activity.
  • Pinpointed a key activation site on TrkB targeted by these antibodies.

Conclusions:

  • TrkB agonist autoantibodies can modulate TrkB signaling pathways.
  • The identified activation site represents a potential target for therapeutic intervention.
  • Findings provide a basis for exploring immune-related mechanisms in breast cancer treatment.
Keywords:
AutoantibodyNTRK2TrkBagonist antibodycancer

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