Evidence map›Paper›PMID 25962108›Full record

ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2015

Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1α-secreting Glioblastoma.

Nadja Müller, Susanne Michen, Stefanie Tietze, Katrin Töpfer, Alexander Schulte, Katrin Lamszus, Marc Schmitz, Gabriele Schackert, Ira Pastan, Achim Temme

Abstract read
In one paragraph

Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

174 citing papers in PubMed, 241 citations in OpenAlex.

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  14. Precision sniper for solid tumors: CAR-NK cell therapy.Cancer immunology, immunotherapy : CII · 2025
    Review
  15. Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.International journal of molecular sciences · 2025
    Review
  16. Review
  17. 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
  18. Article
  19. Review
  20. Article

114 more citing papers are in PubMed but not listed here.

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 4 institutions in 3 countries.

Nadja Müller*Department of Neurosurgery, Section Experimental Neurosurgery/Tumor Immunology, University Hospital Carl Gustav Carus ‡Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden §German Cancer Consortium (DKTK), Dresden †Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ∥Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Susanne Michen
Stefanie Tietze
Katrin Töpfer
Alexander Schulte
Katrin Lamszus
Marc Schmitz
Gabriele Schackert
Ira Pastan
Achim Temme
University Hospital Carl Gustav Carus · DEUniversity Medical Center Hamburg-Eppendorf · DEInstitute of Immunology · HRNational Cancer Institute · US

Funding

Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical StudiesZIABC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2024
$33.1M
Growth Regulation SectionZIABC010298 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2023
$5.0M
IMMUNOTOXIN THERAPY OF SOLID AND HEMATOPOIETIC TUMORS: PRECLINICAL STUDIESZ01BC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 1996 to 2008
$3.2M
Intramural NIH HHS Z01 BC008753
6 · The paper itself

Abstract

Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1α secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.

Indexed as

Gene ExpressionImmunotherapyAnimalsCell- and Tissue-Based TherapyCell LineChemokine CXCL12ChemotaxisCytotoxicity, ImmunologicDisease Models, AnimalEctopic Gene ExpressionErbB ReceptorsFemaleGene OrderGenetic TherapyGenetic VectorsGlioblastomaChemokine CXCL12epidermal growth factor receptor VIIIErbB ReceptorsReceptors, Antigen, T-CellReceptors, CXCR4Recombinant Fusion Proteins

Identifiers

PMID25962108
PMCPMC4428685
OpenAlexW2402659606

What OpenQuestion holds

Textmetadata
LicenceTDM
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.