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Updated: Aug 5, 2026
09:54
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Next-Generation Multi-Engager Complexes Linking Natural Killer Cells to Tumor Cells and Targeting the Proteolytic
Kate J Dixon1, Bruce Walcheck1,2,3,4
1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.
Cells
|July 27, 2026
Summary
Natural killer (NK) cells fight tumors via antibody-dependent cellular cytotoxicity (ADCC). Inhibiting ADAM17 may enhance NK cell therapies by preventing CD16 receptor loss, boosting anti-cancer activity.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Natural killer (NK) cells are crucial innate immune cells for tumor surveillance.
- Antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells relies on CD16 (FcγRIIIA) engagement.
- Multi-engager complexes aim to enhance NK cell-mediated tumor killing.
Purpose of the Study:
- To review NK cell biology and the role of ADAM17 in NK cell function and tumor growth.
- To examine the clinical development of NK cell multi-engager complexes.
- To discuss strategies for inhibiting ADAM17 to improve therapeutic efficacy.
Main Methods:
- Literature review of NK cell biology, ADCC mechanisms, and ADAM17 function.
- Analysis of multi-engager complexes in clinical development.
- Exploration of ADAM17 inhibition as a therapeutic strategy.
Main Results:
- NK cell CD16 expression is downregulated by ADAM17 upon activation, reducing ADCC.
- The tumor microenvironment exacerbates CD16 downregulation, impairing NK cell anti-tumor activity.
- ADAM17 is upregulated in tumors, promoting tumor growth and releasing NK cell ligands.
Conclusions:
- ADAM17 inhibition is a critical strategy to enhance NK cell-based immunotherapies.
- Blocking ADAM17 can restore CD16 expression and improve ADCC potency.
- Targeting ADAM17 holds promise for optimizing multi-engager complex efficacy and suppressing tumor growth.
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