Evidence map›Paper›PMID 33375774›Full record

ArticleHaematologica2022

CD38 knockout natural killer cells expressing an affinity optimized CD38 chimeric antigen receptor successfully target acute myeloid leukemia with reduced effector cell fratricide.

Mark Gurney, Arwen Stikvoort, Emma Nolan, Lucy Kirkham-McCarthy, Stanislav Khoruzhenko, Rama Shivakumar, Sonja Zweegman, Niels W C J Van de Donk, Tuna Mutis, Eva Szegezdi and 2 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

76 citing papers in PubMed, 108 citations in OpenAlex.

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  13. Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  16. The clinical landscape of CAR NK cells.Experimental hematology & oncology · 2025
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16 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

12 authors at 5 institutions in 3 countries.

Mark GurneyNational University of Ireland Galway, Galway.
Arwen StikvoortCancer Center Amsterdam, VU University Medical Center, Amsterdam.
Emma NolanNational University of Ireland Galway, Galway.
Lucy Kirkham-McCarthyNational University of Ireland Galway, Galway.
Stanislav KhoruzhenkoMaxCyte, Inc., Maryland.
Rama ShivakumarMaxCyte, Inc., Maryland.
Sonja ZweegmanCancer Center Amsterdam, VU University Medical Center, Amsterdam.
Niels W C J Van de DonkCancer Center Amsterdam, VU University Medical Center, Amsterdam.
Tuna MutisCancer Center Amsterdam, VU University Medical Center, Amsterdam.
Eva SzegezdiNational University of Ireland Galway, Galway.
Subhashis SarkarNational University of Ireland Galway, Galway.
Michael O'DwyerNational University of Ireland Galway, Galway. michael.odwyer@nuigalway.ie.
Ollscoil na Gaillimhe – University of Galway · IEMaxCyte (United States) · USUniversity Hospital and Clinics · USAmsterdam UMC Location VUmc · NLUniversity Medical Center · US

Funding

Wellcome Trust
6 · The paper itself

Abstract

There is a strong biological rationale for the augmentation of allogeneic natural killer (NK) cell therapies with a chimeric antigen receptor (CAR) to enhance acute myeloid leukemia (AML) targeting. CD38 is an established immunotherapeutic target in multiple myeloma and under investigation as a target antigen in AML. CD38 expression on NK cells and its further induction during ex vivo NK cell expansion represents a barrier to the development of a CD38 CAR-NK cell therapy. We set out to develop a CD38 CAR-NK cell therapy for AML, first by using an NK cell line which has low baseline CD38 expression and subsequently healthy donor expanded NK cells. To overcome anticipated fratricide due to NK cell CD38 expression when using primary expanded NK cells, we applied CRISPR/Cas9 genome editing to disrupt the CD38 gene during expansion achieving a mean knockdown efficiency of 84%. The resulting CD38 KD expanded NK cells, after expression of an affinity optimized CD38 CAR, showed reduced NK cell fratricide and an enhanced ability to target primary AML blasts. Furthermore, the cytotoxic potential of CD38 CAR-NK cells was augmented by pre-treatment of the AML cells with all-trans retinoic acid which drove enhanced CD38 expression offering a rational combination therapy. These findings support the further investigation of CD38 KD - CD38 CAR-NK cells as a viable immunotherapeutic approach to the treatment of AML.

Indexed as

Immunotherapy, AdoptiveLeukemia, Myeloid, AcuteReceptors, Chimeric AntigenADP-ribosyl Cyclase 1Cell Line, TumorCytotoxicity, ImmunologicGene Knockout TechniquesHumansKiller Cells, NaturalMembrane GlycoproteinsADP-ribosyl Cyclase 1CD38 protein, humanMembrane GlycoproteinsReceptors, Chimeric Antigen

Identifiers

PMID33375774
PMCPMC8804573
OpenAlexW3115869600

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.