Evidence map›Paper›PMID 41694365›Full record

ArticleFrontiers in immunology2026

Dual-functioning Targeted ADAM17 Blocker CD16 (TAB16) mediates selective ADAM17 inhibition in NK cells and engages overexpressed ADAM17 in tumor cells to induce cytotoxicity.

Kate J Dixon, Robert Hullsiek, Sam Wang, Ryan R Friess, Anders W Matson, Yvette Soignier, Alexander J Lenvik, Jianming Wu, Geoffrey T Hart, Martin Felices and 1 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kate J DixonDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.
Robert Hullsiek *Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.
Sam WangDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.
Ryan R FriessDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.
Anders W MatsonMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.
Yvette SoignierMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.
Alexander J LenvikMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.
Jianming WuDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.
Geoffrey T HartDepartment of Medicine, University of Minnesota, Minneapolis, MN, United States.
Martin FelicesMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.
Bruce WalcheckDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.

Funding

Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UM1TR004405 · NCATS · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar, Damien A Fair · 2023 to 2026
$30.8M
Expression of recombinant Fc receptors by engineered NK cells to enhance cancer cell killingR01CA203348 · NCI · UNIVERSITY OF MINNESOTA · PI WALCHECK, BRUCE K, WU, JIANMING · 2016 to 2025
$4.4M
Targeting off-the-shelf iPSC-derived natural killer cells against solid tumorsR35CA283892 · NCI · UNIVERSITY OF MINNESOTA · PI Jeffrey S. Miller · 2023 to 2026
$3.7M
CTSA Postdoctoral T32 at University of MinnesotaT32TR004376 · NCATS · UNIVERSITY OF MINNESOTA · PI Jayne Allyn Fulkerson · 2024 to 2026
$1.1M
NCATS NIH HHS T32 TR004376NCATS NIH HHS UM1 TR004405NCI NIH HHS P01 CA111412NCI NIH HHS R01 CA203348NCI NIH HHS R35 CA283892
6 · The paper itself

Abstract

Introduction: Natural killer (NK) cells are innate lymphocytes that kill tumor cells by natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). Human NK cells mediate the latter process exclusively by the IgG Fc receptor CD16 (FcγRIIIA). Cell surface levels of this activating receptor are tightly regulated by the metalloprotease ADAM17, which cleaves CD16 upon NK cell activation or cellular stress. We have reported that Medi-1, a fully human IgG1 mAb, blocks ADAM17, and its Fc region is simultaneously engaged by CD16, inducing and prolonging its signaling, which synergizes with cytokine stimulation, such as IL-15. To exploit these distinctive features of Medi-1 while also addressing limitations of the mAb, such as the varied affinity by which CD16 binds to it due to receptor polymorphisms and the risk of broadly blocking ADAM17 activity, we engineered Targeted ADAM17 Blocker CD16 (TAB16). Methods: TAB16 was generated with a camelid heavy-chain variable domain specific to CD16 linked to a single-chain variable fragment derived from Medi-1. TAB16 was further modified by the linkage of an IL-15 moiety to generate TAB16/15. Primary human NK cells were treated with TAB16 or TAB16/15 and evaluated for proliferation by cell dilution dye, ADAM17 blocking, activation marker expression, and cytotoxicity against ovarian cancer cell lines in real-time by IncuCyte assays. Results: The TAB16 bispecific engager targeted NK cells and blocked ADAM17. A novel feature of TAB16 is its dual functionality, as it synergizes with IL-15 to enhance NK cell activation and proliferation and targets ADAM17 overexpressed on cancer cells to induce ADCC. TAB16 is a modifiable backbone to which additional functional components can be added, such as IL-15 (TAB16/15) for consolidated and multifaceted activity. Discussion: Our ADAM17-engaging platform offers a unique approach for targeted ADAM17 inhibition to augment the anti-tumor function of endogenous and therapeutic NK cells.

Indexed as

ADAM17 ProteinKiller Cells, NaturalOvarian NeoplasmsReceptors, IgGAntibody-Dependent Cell CytotoxicityCell Line, TumorCytotoxicity, ImmunologicFemaleGPI-Linked ProteinsHumansADAM17 ProteinADAM17 protein, humanFCGR3B protein, humanGPI-Linked ProteinsReceptors, IgGADAM17 (a disintegrin and metalloprotease 17)ADCC - antibody-dependent cellular cytotoxicityimmunotherapynatural killer (NK) cellovarian cancer

Identifiers

PMID41694365
PMCPMC12901421

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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.