ArticlePloS one2015
Identification of an ADAM17 cleavage region in human CD16 (FcγRIII) and the engineering of a non-cleavable version of the receptor in NK cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 149 citations in OpenAlex.
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Review
- ADAM17 blockade restores natural killer cell antibody-dependent cytotoxicity against human immunodeficiency virus-1.Virology journal · 2026Article
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- Engineering Bi-Specific CAR-NK Cells to Restore Antibody-Dependent Cellular Cytotoxicity in Solid Tumors.Cells · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- A glycoengineered anti-ROR1 antibody, GE-zilovertamab, selectively enhances antibody-dependent cellular cytotoxicity against chronic lymphocytic leukemia.Antibody therapeutics · 2026Article
- Dual-functioning Targeted ADAM17 Blocker CD16 (TAB16) mediates selective ADAM17 inhibition in NK cells and engages overexpressed ADAM17 in tumor cells to induce cytotoxicity.Frontiers in immunology · 2026Article
- Overcoming barriers in CAR-NK immunotherapy: CRISPR-Driven advances in checkpoint editing and allogeneic design.Functional & integrative genomics · 2025Review
- Review
- Multiplexed iPSC platform for advanced NK cell immunotherapies.Cell reports. Medicine · 2025Review
- A monoclonal antibody that inhibits the shedding of CD16a and CD16b and promotes antibody-dependent cellular cytotoxicity against tumors.Nature communications · 2025Article
- iPSC-derived trimodal T cells engineered with CAR, TCR, and hnCD16 modalities can overcome antigen escape in heterogeneous tumors.Cell reports. Medicine · 2025Article
- Precision enhancement of CAR-NK cells through non-viral engineering and highly multiplexed base editing.Journal for immunotherapy of cancer · 2025Article
- Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Adoptive Cell Therapy from the Dish: Potentiating Induced Pluripotent Stem Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Gene-modified NK cells expressing CD64 and preloaded with HIV-specific BNAbs target autologous HIV-1-infected CD4+ T cells by ADCC.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.Life medicine · 2025Review
- CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.Cell reports. Medicine · 2025Article
- Discovery and early validation of serum protein signatures in untreated multiple sclerosis patients: identification of candidate biomarkers for diagnosis and stratification.Frontiers in immunology · 2025Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
CD16a and CD16b are IgG Fc receptors expressed by human natural killer (NK) cells and neutrophils, respectively. Both CD16 isoforms undergo a rapid down-regulation in expression by ADAM17-mediated proteolytic cleavage upon cell activation by various stimuli. We examined soluble CD16 released from activated NK cells and neutrophils by mass spectrometric analysis, and identified three separate cleavage sites in close proximity at P1/P1' positions alanine195/valine196, valine196/serine197, and threonine198/isoleucine199, revealing a membrane proximal cleavage region in CD16. Substitution of the serine at position 197 in the middle of the cleavage region for a proline (S197P) effectively blocked CD16a and CD16b cleavage in cell-based assays. We also show that CD16a/S197P was resistant to cleavage when expressed in the human NK cell line NK92 and primary NK cells derived from genetically-engineered human induced pluripotent stem cells. CD16a is a potent activating receptor and despite blocking CD16a shedding, the S197P mutation did not disrupt IgG binding by the receptor or its activation of NK92 cells by antibody-treated tumor cells. Our findings provide further characterization of CD16 cleavage by ADAM17 and they demonstrate that a non-cleavable version of CD16a can be expressed in engineered NK cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.