ArticleCancer immunology, immunotherapy : CII2018
Anti-ADAM17 monoclonal antibody MEDI3622 increases IFNγ production by human NK cells in the presence of antibody-bound tumor cells.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- 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
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- A monoclonal antibody that inhibits the shedding of CD16a and CD16b and promotes antibody-dependent cellular cytotoxicity against tumors.Nature communications · 2025Article
- CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells.European journal of immunology · 2025Article
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ.Frontiers in immunology · 2025Review
- Review
- Reprogramming natural killer cells for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Natural Killer cells at the frontline in the fight against cancer.Cell death & disease · 2024Review
- Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Review
- Inhibiting N-glycan processing increases the antibody binding affinity and effector function of human natural killer cells.Immunology · 2023Article
- The role of EphA2 in ADAM17- and ionizing radiation-enhanced lung cancer cell migration.Frontiers in oncology · 2023Article
- Antibody Fc-chimerism and effector functions: When IgG takes advantage of IgA.Frontiers in immunology · 2023Review
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse Model.Frontiers in immunology · 2022Article
- Examination of IgG Fc Receptor CD16A and CD64 Expression by Canine Leukocytes and Their ADCC Activity in Engineered NK Cells.Frontiers in immunology · 2022Article
- CRISPR Gene Editing of Human Primary NK and T Cells for Cancer Immunotherapy.Frontiers in oncology · 2022Review
- From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement.Frontiers in immunology · 2022Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Several clinically successful tumor-targeting mAbs induce NK cell effector functions. Human NK cells exclusively recognize tumor-bound IgG by the FcR CD16A (FcγRIIIA). Unlike other NK cell activating receptors, the cell surface density of CD16A can be rapidly downregulated in a cis manner by the metalloproteinase ADAM17 following NK cell stimulation in various manners. CD16A downregulation takes place in cancer patients and this may affect the efficacy of tumor-targeting mAbs. We examined the effects of MEDI3622, a human mAb and potent ADAM17 inhibitor, on NK cell activation by antibody-bound tumor cells. MEDI3622 effectively blocked ADAM17 function in NK cells and caused a marked increase in their production of IFNγ. This was observed for NK cells exposed to different tumor cell lines and therapeutic antibodies, and over a range of effector/target ratios. The augmented release of IFNγ by NK cells was reversed by a function-blocking CD16A mAb. In addition, NK92 cells, a human NK cell line that lacks endogenous FcγRs, expressing a recombinant non-cleavable version of CD16A released significantly higher levels of IFNγ than NK92 cells expressing equivalent levels of wildtype CD16A. Taken together, our data show that MEDI3622 enhances the release of IFNγ by NK cells engaging antibody-bound tumor cells by blocking the shedding of CD16A. These findings support ADAM17 as a dynamic inhibitory checkpoint of the potent activating receptor CD16A, which can be targeted by MEDI3622 to potentially increase the efficacy of anti-tumor therapeutic antibodies.
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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.