Evidence map›Paper›PMID 32303428›Full record

Trial reportCytotherapy2020

Fc-engineered anti-CD33 monoclonal antibody potentiates cytotoxicity of membrane-bound interleukin-21 expanded natural killer cells in acute myeloid leukemia.

Rajeswaran Mani, Girish Rajgolikar, Jessica Nunes, Kevan Zapolnik, Ronni Wasmuth, Xiaokui Mo, John C Byrd, Dean A Lee, Natarajan Muthusamy, Sumithira Vasu

Open access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cytotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
1.1field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Advances in NK cell production.Cellular & molecular immunology · 2022
    Review
  11. Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021
    Review
  12. Review
  13. Review
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 2 institutions in 1 country.

Rajeswaran ManiComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Girish RajgolikarComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Jessica NunesComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Kevan ZapolnikComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Ronni WasmuthComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Xiaokui MoCenter for Biostatistics, The Ohio State University, Columbus, Ohio, USA.
John C ByrdComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Dean A LeeComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA; Nationwide Children's Hospital, Columbus, Ohio, USA.
Natarajan MuthusamyComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address: raj.muthusamy@osumc.edu.
Sumithira VasuComprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address: sumithira.vasu@osumc.edu.
The Ohio State University · USNationwide Children's Hospital · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3M
Targeted Therapy for LeukemiaR35CA197734 · NCI · UNIVERSITY OF CINCINNATI · PI BYRD, JOHN C. · 2015 to 2021
$6.6M
NCI NIH HHS P30 CA016058NCI NIH HHS R35 CA197734
6 · The paper itself

Abstract

backgroundQualitative and quantitative defects in natural killer (NK) cells have been noted in patients with acute myeloid leukemia (AML), providing rationale for infusion of donor-derived NK cells. We previously showed that decitabine enhances expression of NKG2D ligands in AML with additive cytotoxicity when NK cells and Fc (fragment crystallizable region)-engineered CD33 monoclonal antibody (CD33mAb) was used. We conducted a phase 1 study evaluating decitabine and haploidentical NK cells in relapsed AML. Using patient samples from this study, we evaluated whether ex vivo donor-derived expanded NK cells with or without CD33mAb was effective in decitabine-treated AML.

methodsBone marrow aspirates were collected from patients at pre- and post-NK cell infusion. NK cells from healthy donors were expanded for 14 days using irradiated K562 feeder cells displaying membrane-bound IL-21 (mbIL-21). Patient samples were used to test in vitro activity of mbIL-21 NK cells ± CD33m Ab-dependent cellular cytotoxicity (ADCC) and AML patient derived xenograft (PDX) mice were developed to test in vivo activity.

resultsUpon incubation with primary AML blasts, mbIL-21 NK cells showed variable donor-dependent intra-cellular interferon-γ production, which increased with CD33mAb-coated AML. ADCC assays revealed mbIL-21 NK cells effectively lysed primary AML blasts with higher activity on CD33mAb-coated AML. Importantly, CD33mAb-dependent enhanced cytotoxicity by mbIL-21 NK cells was maintained in AML cells from patients even 24 days post-decitabine treatment. In vivo infusion of mbIL-21 NK cells in AML PDX mice, treated with CD33mAb, reduced the tumor burden. DISCUSSION: These data show the therapeutic utility of mbIL-21 NK cells that can be further potentiated by addition of CD33mAb in AML.

Indexed as

AgedAnimalsAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCell Line, TumorCell MembraneCytotoxicity, ImmunologicFemaleHumansImmunoglobulin Fc FragmentsInterleukin-2Interleukin-21InterleukinsKiller Cells, NaturalLeukemia, Myeloid, AcuteLymphocyte ActivationAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalfludarabineImmunoglobulin Fc FragmentsInterleukin-2Interleukin-21InterleukinsSialic Acid Binding Ig-like Lectin 3Vidarabineacute myeloid leukemiaantibody-dependent cellular cytotoxicityCD33 antibodyinterleukin-21membrane-bound interleukin-21 natural killer cellsnatural killer cellular therapy

Identifiers

PMID32303428
PMCPMC8176194
OpenAlexW3016787150

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.