Evidence map›Paper›PMID 38334638›Full record

ArticleCells2024

Dual Targeting of Glioblastoma Cells with Bispecific Killer Cell Engagers Directed to EGFR and ErbB2 (HER2) Facilitates Effective Elimination by NKG2D-CAR-Engineered NK Cells.

Anne Kiefer, Maren Prüfer, Jasmin Röder, Jordi Pfeifer Serrahima, Malena Bodden, Ines Kühnel, Pranav Oberoi, Winfried S Wels

Open access · goldAbstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.8field-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

16 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Review
  9. Review
  10. Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
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

8 authors at 2 institutions in 1 country.

Anne KieferGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Maren PrüferGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Jasmin RöderGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Jordi Pfeifer SerrahimaGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Malena BoddenGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Ines KühnelGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Pranav OberoiGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.
Winfried S WelsGeorg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany.ORCID 0000-0001-9858-3643
Georg Speyer Haus · DEGoethe University Frankfurt · DE

Funding

Deutsche Forschungsgemeinschaft WE 2589/6-1LOEWE Center Frankfurt Cancer Institute HMWK III L 5-519/03/03.001-0015
6 · The paper itself

Abstract

NKG2D is an activating receptor of natural killer cells that recognizes stress-induced ligands (NKG2DL) expressed by many tumor cells. Nevertheless, NKG2DL downregulation or shedding can still allow cancer cells to evade immune surveillance. Here, we used lentiviral gene transfer to engineer clinically usable NK-92 cells with a chimeric antigen receptor (NKAR) which contains the extracellular domain of NKG2D for target recognition, or an NKAR, together with the IL-15 superagonist RD-IL15, and combined these effector cells with recombinant NKG2D-interacting bispecific engagers that simultaneously recognize the tumor-associated antigens epidermal growth factor receptor (EGFR) or ErbB2 (HER2). Applied individually, in in vitro cell-killing assays, these NKAB-EGFR and NKAB-ErbB2 antibodies specifically redirected NKAR-NK-92 and NKAR_RD-IL15-NK-92 cells to glioblastoma and other cancer cells with elevated EGFR or ErbB2 levels. However, in mixed glioblastoma cell cultures, used as a model for heterogeneous target antigen expression, NKAR-NK cells only lysed the EGFR- or ErbB2-expressing subpopulations in the presence of one of the NKAB molecules. This was circumvented by applying NKAB-EGFR and NKAB-ErbB2 together, resulting in effective antitumor activity similar to that against glioblastoma cells expressing both target antigens. Our results demonstrate that combining NK cells carrying an activating NKAR receptor with bispecific NKAB antibodies allows for flexible targeting, which can enhance tumor-antigen-specific cytotoxicity and prevent immune escape.

Indexed as

Antibodies, BispecificGlioblastomaCell Line, TumorErbB ReceptorsHumansInterleukin-15Killer Cells, NaturalNK Cell Lectin-Like Receptor Subfamily KAntibodies, BispecificEGFR protein, humanErbB ReceptorsInterleukin-15NK Cell Lectin-Like Receptor Subfamily Kbispecific antibodychimeric antigen receptorEGFRErbB2natural killer cellsNK-92NKG2D

Identifiers

PMID38334638
PMCPMC10854564
OpenAlexW4391313957

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.