Related Experiment Video
Updated: Jun 11, 2026
Generation of Monoclonal Antibodies Against Natural Products
Published on: April 6, 2019
Identification and characterization of a novel agonistic anti-DR4 human monoclonal antibody
Yang Feng1, Xiaodong Xiao, Zhongyu Zhu
1Protein Interactions Group, CCRNP, NCI-Frederick, NIH, Frederick, MD, USA. fengya@mail.nih.gov
Abstract:
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been established as promising targets for cancer treatment. Therapeutics targeting TRAIL and its receptors are not only effective in killing many types of tumors, but they also synergize with traditional therapies and show efficacy against tumors that are otherwise resistant to conventional treatments. We describe here the identification and characterization of two human monoclonal antibodies, m921 and m922, that are specific for human DR4. Both antibodies competed with TRAIL for binding to DR4, but only m921 recognized cell surface-associated DR4 and inhibited the growth of ST486 cells. This antibody may have potential for further development as a candidate therapeutic and research tool.
Insights
Two new monoclonal antibodies, m921 and m922, target the DR4 receptor for cancer therapy. Antibody m921 shows potential for treating resistant tumors by inhibiting cell growth.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (DR4, DR5) are key targets in cancer therapy.
- TRAIL-targeted therapeutics offer efficacy against various tumors, including those resistant to conventional treatments.
- These therapies can synergize with existing cancer treatments.
Purpose of the Study:
- To identify and characterize novel human monoclonal antibodies targeting the DR4 receptor.
- To evaluate the therapeutic potential of these antibodies in cancer treatment.
Main Methods:
- Identification and characterization of two human monoclonal antibodies, m921 and m922.
- Assessment of antibody binding to DR4 and competition with TRAIL.
- Evaluation of antibody-mediated inhibition of cancer cell growth (ST486 cells).
Main Results:
- Both m921 and m922 antibodies bind specifically to human DR4.
- Both antibodies compete with TRAIL for binding to DR4.
- Antibody m921 recognizes cell surface DR4 and inhibits the growth of ST486 cancer cells.
Conclusions:
- Antibody m921 demonstrates potential as a therapeutic agent for cancer treatment.
- m921 may serve as a valuable research tool for studying DR4-mediated apoptosis.
- Further development of m921 is warranted for its therapeutic applications.
