Evidence map›Paper›PMID 35546150›Full record

ArticleNature communications2022

Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19.

Ting Lu, Rui Ma, Wenjuan Dong, Kun-Yu Teng, Daniel S Kollath, Zhiyao Li, Jinhee Yi, Christian Bustillos, Shoubao Ma, Lei Tian and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.8field-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

33 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
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  7. Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Review
  8. Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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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

18 authors at 2 institutions in 1 country.

Ting Lu *Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Rui Ma *Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Wenjuan Dong *Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Kun-Yu TengDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Daniel S KollathPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Zhiyao LiDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Jinhee YiPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Christian BustillosDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Shoubao MaDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Lei TianDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Anthony G MansourDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Zhenlong LiDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Erik W SettlesPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0003-4331-3683
Jianying ZhangDepartment of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Paul S KeimPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0003-0089-5820
Bridget M BarkerPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0002-3439-4517
Michael A CaligiuriDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.ORCID 0000-0002-4095-3020
Jianhua YuDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.ORCID 0000-0002-0326-3223
City Of Hope National Medical Center · USNorthern Arizona University · US

Funding

The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2013 to 2026
$26.0M
Human natural killer cells: Advancing biology and clinical applicationsR35CA210087 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2017 to 2026
$8.3M
IL-15--CHARACTERIZATION THROUGH EXPERIMENTAL IMMUNOLOGYR01CA068458 · NCI · ROSWELL PARK CANCER INSTITUTE · PI CALIGIURI, MICHAEL A, YU, JIANHUA · 1996 to 2019
$4.5M
Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid LeukemiaR01CA265095 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BUDDE, LIHUA ELIZABETH, CALIGIURI, MICHAEL A · 2021 to 2025
$2.4M
Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK CellsR01CA247550 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, JIANHUA · 2020 to 2024
$2.2M
Elucidate and Modulate Cell Signaling in NK Cells for Glioma TreatmentR01AI129582 · NIAID · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2017 to 2021
$2.1M
Overcoming Barriers of Virotherapy by Next-Generation oHSV Expressing E-CadherinR01NS106170 · NINDS · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2018 to 2023
$1.9M
Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint InhibitorsR01CA266457 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI VILLALONA, MIGUEL A, YU, JIANHUA · 2022 to 2025
$1.8M
scFvPD1-FLT3 CAR T Cells for the Treatment of Relapsed Acute Myeloid LeukemiaR21CA223400 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, JIANHUA · 2019 to 2020
$414k
NCI NIH HHS P01 CA163205NCI NIH HHS R01 CA068458NCI NIH HHS R01 CA247550NCI NIH HHS R01 CA265095NCI NIH HHS R01 CA266457NCI NIH HHS R21 CA223400NCI NIH HHS R35 CA210087NIAID NIH HHS R01 AI129582NINDS NIH HHS R01 NS106170
6 · The paper itself

Abstract

Engineered natural killer (NK) cells represent a promising option for immune therapy option due to their immediate availability in allogeneic settings. Severe acute diseases, such as COVID-19, require targeted and immediate intervention. Here we show engineering of NK cells to express (1) soluble interleukin-15 (sIL15) for enhancing their survival and (2) a chimeric antigen receptor (CAR) consisting of an extracellular domain of ACE2, targeting the spike protein of SARS-CoV-2. These CAR NK cells (mACE2-CAR_sIL15 NK cells) bind to VSV-SARS-CoV-2 chimeric viral particles as well as the recombinant SARS-CoV-2 spike protein subunit S1 leading to enhanced NK cell production of TNF-α and IFN-γ and increased in vitro and in vivo cytotoxicity against cells expressing the spike protein. Administration of mACE2-CAR_sIL15 NK cells maintains body weight, reduces viral load, and prolongs survival of transgenic mice expressing human ACE2 upon infection with live SARS-CoV-2. These experiments, and the capacity of mACE2-CAR_sIL15 NK cells to retain their activity following cryopreservation, demonstrate their potential as an allogeneic off-the-shelf therapy for COVID-19 patients who are faced with limited treatment options.

Indexed as

COVID-19Receptors, Chimeric AntigenAngiotensin-Converting Enzyme 2AnimalsHumansInterleukin-15Killer Cells, NaturalMiceSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Interleukin-15Receptors, Chimeric AntigenSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID35546150
PMCPMC9095674
OpenAlexW4280637790

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.