Evidence map›Paper›PMID 34599028›Full record

ArticleJournal for immunotherapy of cancer2021

Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity.

Congcong Zhang, Jasmin Röder, Anne Scherer, Malena Bodden, Jordi Pfeifer Serrahima, Anita Bhatti, Anja Waldmann, Nina Müller, Pranav Oberoi, Winfried S Wels

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
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

45 citing papers in PubMed, 61 citations in OpenAlex.

  1. IL-15/NKG2D signaling-mediated activation of CD8Journal of thoracic disease · 2026
    Article
  2. Review
  3. Review
  4. A Novel MICB-Targeting CAR-NK Cells for the Treatment of Pancreatic Cancer.International journal of molecular sciences · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  9. Article
  10. Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Reprogramming natural killer cells for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  19. Article
  20. NK cells as powerful therapeutic tool in cancer immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2024
    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

10 authors at 3 institutions in 1 country.

Congcong ZhangGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Jasmin RöderGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Anne SchererGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Malena BoddenGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Jordi Pfeifer SerrahimaGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Anita BhattiGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Anja WaldmannGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Nina MüllerGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Pranav OberoiGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.
Winfried S WelsGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany wels@gsh.uni-frankfurt.de.ORCID 0000-0001-9858-3643
Georg Speyer Haus · DEGoethe University Frankfurt · DEGerman Cancer Research Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNatural killer group 2D (NKG2D) is an activating receptor of natural killer (NK) cells and other lymphocytes that mediates lysis of malignant cells through recognition of stress-induced ligands such as MICA and MICB. Such ligands are broadly expressed by cancer cells of various origins and serve as targets for adoptive immunotherapy with effector cells endogenously expressing NKG2D or carrying an NKG2D-based chimeric antigen receptor (CAR). However, shedding or downregulation of NKG2D ligands (NKG2DL) can prevent NKG2D activation, resulting in escape of cancer cells from NKG2D-dependent immune surveillance.

methodsTo enable tumor-specific targeting of NKG2D-expressing effector cells independent of membrane-anchored NKG2DLs, we generated a homodimeric recombinant antibody which harbors an N-terminal single-chain fragment variable (scFv) antibody domain for binding to NKG2D, linked via a human IgG

resultsOn its own, bispecific NKAB-ErbB2 increased lysis of ErbB2-positive breast carcinoma cells by peripheral blood-derived NK cells endogenously expressing NKG2D more effectively than an ErbB2-specific IgG

conclusionsOur results demonstrate that combining an NKAB antibody with effector cells expressing an activating NKAR receptor represents a powerful and versatile approach to simultaneously enhance tumor antigen-specific as well as NKG2D-CAR and natural NKG2D-mediated cytotoxicity, which may be particularly useful to target tumors with heterogeneous target antigen expression.

Indexed as

AnimalsAntibodies, BispecificCell Line, TumorDisease Models, AnimalFemaleHumansImmunotherapyKiller Cells, NaturalMiceNeoplasmsNK Cell Lectin-Like Receptor Subfamily KReceptors, Chimeric AntigenAntibodies, BispecificNK Cell Lectin-Like Receptor Subfamily KReceptors, Chimeric Antigenadoptiveantibodieschimeric antigenimmunotherapykiller cellsnaturalneoplasmreceptors

Identifiers

PMID34599028
PMCPMC8488744
OpenAlexW3201812987

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

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.