Evidence map›Paper›PMID 38690288›Full record

ArticleFrontiers in immunology2024

Self-sufficient primary natural killer cells engineered to express T cell receptors and interleukin-15 exhibit improved effector function and persistence.

Els P van Hees, Laura T Morton, Dennis F G Remst, Anne K Wouters, Astrid Van den Eynde, J H Frederik Falkenburg, Mirjam H M Heemskerk

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Els P van HeesDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Laura T MortonDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Dennis F G RemstDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Anne K WoutersDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Astrid Van den EyndeCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), Antwerp, Belgium.
J H Frederik FalkenburgDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Mirjam H M HeemskerkDepartment of Hematology, Leiden University Medical Centre (LUMC), Leiden, Netherlands.
Leiden University Medical Center · NLIntegrated Oncology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: NK cells can be genetically engineered to express a transgenic T-cell receptor (TCR). This approach offers an alternative strategy to target heterogenous tumors, as NK:TCR cells can eradicate both tumor cells with high expression of HLA class I and antigen of interest or HLA class I negative tumors. Expansion and survival of NK cells relies on the presence of IL-15. Therefore, autonomous production of IL-15 by NK:TCR cells might improve functional persistence of NK cells. Here we present an optimized NK:TCR product harnessed with a construct encoding for soluble IL-15 (NK:TCR/IL-15), to support their proliferation, persistence and cytotoxic capabilities. Methods: Expression of tumor-specific TCRs in peripheral blood derived NK-cells was achieved following retroviral transduction. NK:TCR/IL-15 cells were compared with NK:TCR cells for autonomous cytokine production, proliferation and survival. NK:BOB1-TCR/IL-15 cells, expressing a HLA-B*07:02-restricted TCR against BOB1, a B-cell lineage specific transcription factor highly expressed in all B-cell malignancies, were compared with control NK:BOB1-TCR and NK:CMV-TCR/IL-15 cells for effector function against TCR antigen positive malignant B-cell lines Results: Viral incorporation of the interleukin-15 gene into engineered NK:TCR cells was feasible and high expression of the TCR was maintained, resulting in pure NK:TCR/IL-15 cell products generated from peripheral blood of multiple donors. Self-sufficient secretion of IL-15 by NK:TCR cells enables engineered NK cells to proliferate Conclusion: This study showed that NK:TCR/IL-15 cells secrete low levels of IL-15 and can proliferate in an environment lacking cytokines. Repeated

Indexed as

Interleukin-15Killer Cells, NaturalReceptors, Antigen, T-CellAnimalsCell Line, TumorCell ProliferationCytotoxicity, ImmunologicGenetic EngineeringHumansImmunotherapy, AdoptiveMiceIL15 protein, humanInterleukin-15Receptors, Antigen, T-CellBob1cancerimmunotherapyinterleukin-15multiple myelomaNK cellsT-cell receptor

Identifiers

PMID38690288
PMCPMC11058644
OpenAlexW4394850262

What OpenQuestion holds

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Registered trials

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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.