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Updated: Sep 18, 2025

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method
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Design of TNFR peptide agonists for inducing receptor oligomerization and cell apoptosis

Yi-Xuan Liu1,2, Hao Wang1,2

  • 1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), Beijing, 100190, China. wanghao@nanoctr.cn.

Chemical Communications (Cambridge, England)
|June 25, 2025
PubMed

Insights

Researchers developed novel peptide agonists targeting Tumor Necrosis Factor Receptors (TNFRs) to combat chemotherapy-resistant cancers. These peptides induce apoptosis in cancer cells, showing significant therapeutic potential.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cancer Therapeutics
  • Drug Discovery

Background:

  • Tumor Necrosis Factor Receptors (TNFRs) are crucial in cancer therapy, especially for drug-resistant cells inducing p53-independent apoptosis.
  • Targeting TNFRs offers a promising strategy for overcoming treatment resistance in malignancies.

Purpose of the Study:

  • To design and characterize novel peptide agonists targeting CD95 and death receptor 5 (DR5) for cancer treatment.
  • To investigate the therapeutic potential of these peptides against treatment-resistant cancer cells.

Main Methods:

  • Utilized beta-sheet structures from FasL and TRAIL as scaffolds for peptide design.
  • Employed computational design and AlphaFold3 analysis to identify lead peptides (W10, AP, EIA, EPR).
  • Assessed binding affinities (bio-layer interferometry), conformational changes (circular dichroism), specificity, and cellular efficacy (IC50 values).

Main Results:

  • Identified four lead peptides with nanomolar to micromolar binding affinities for CD95 and DR5.
  • Confirmed target specificity and nanocluster formation upon receptor engagement.
  • Demonstrated micromolar IC50 values against colorectal and breast cancer cell lines, inducing NF-κB translocation and apoptosis.

Conclusions:

  • Developed a novel ligand-derived scaffold approach for creating TNFR peptide agonists.
  • These peptides show significant therapeutic potential against treatment-resistant malignancies.
  • The strategy offers a new avenue for developing targeted cancer therapies.

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