Evidence map›Paper›PMID 27013443›Full record

ArticleBlood2016

Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts.

Sumithira Vasu, Shun He, Carolyn Cheney, Bhavani Gopalakrishnan, Rajeswaran Mani, Gerard Lozanski, Xiaokui Mo, Veronica Groh, Susan P Whitman, Renate Konopitzky and 12 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03941496 (Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy), which is not on this map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.6field-weighted citation impact, top 4% 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.

NCT03941496 phase1 / phase2withdrawnnot on this mapstarted 2022, after this paper: background citation

Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy

TypeinterventionalSponsorAndrew DinardoRan2022 to 2023Enrolled0ConditionsTuberculosis, PulmonaryArmsAzacitidine Injection
3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 89 citations in OpenAlex.

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  9. Adoptive NK cell therapy in AML: progress and challenges.Clinical and experimental medicine · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 3 countries.

Sumithira VasuDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.ORCID 0000-0002-5374-5888
Shun HeDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.ORCID 0000-0002-8389-9001
Carolyn CheneyDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Bhavani GopalakrishnanDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Rajeswaran ManiDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Gerard LozanskiDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Xiaokui MoCenter for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH;
Veronica GrohClinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA;
Susan P WhitmanDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Renate KonopitzkyResearch Oncology, Boehringer Ingelheim RCV, Vienna, Austria;
Christian KösslResearch Oncology, Boehringer Ingelheim RCV, Vienna, Austria;
Donna BucciDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
David M LucasDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Jianhua YuDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Michael A CaligiuriDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
William BlumDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
Paul J AdamResearch Oncology, Boehringer Ingelheim RCV, Vienna, Austria;
Eric BorgesResearch Oncology, Boehringer Ingelheim RCV, Vienna, Austria;
Bjoern RueterMedicine Oncology, Boehringer Ingelheim Pharma GmbH, Biberach/Riss, Germany; and.
Karl-Heinz HeiderResearch Oncology, Boehringer Ingelheim RCV, Vienna, Austria;
Guido MarcucciHematologic Malignancies and Stem Cell Transplantation Institute, City of Hope, Duarte, CA.
Natarajan MuthusamyDivision of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, and.
The Ohio State University · USBoehringer Ingelheim (Austria) · ATBoehringer Ingelheim (Germany) · DECity of Hope · USUniversity of Washington · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI WANCAI YANG · 1985 to 2026
$132.3M
TWO SIGNAL REQUIREMENT FOR NATURAL KILLER IMMUNITYP01CA095426 · NCI · OHIO STATE UNIVERSITY · PI CARSON, WILLIAM E. · 2002 to 2016
$29.6M
IL-15--CHARACTERIZATION THROUGH EXPERIMENTAL IMMUNOLOGYR01CA068458 · NCI · ROSWELL PARK CANCER INSTITUTE · PI CALIGIURI, MICHAEL A, YU, JIANHUA · 1996 to 2019
$4.5M
Validation of microRNAs as therapeutic targets in hematological malignanciesR01CA135332 · NCI · OHIO STATE UNIVERSITY · PI MARCUCCI, GUIDO, MUTHUSAMY, NATARAJAN · 2011 to 2015
$1.6M
IL-15 characterization through experimental immunologyR37CA068458 · NCI · OHIO STATE UNIVERSITY · PI CALIGIURI, MICHAEL A · 2010 to 2014
$1.4M
NCI NIH HHS P01 CA095426NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA068458NCI NIH HHS R01 CA135332NCI NIH HHS R37 CA068458
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML. Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets. BI 836858-opsonized AML cells significantly induced both autologous and allogeneic natural killer (NK)-cell degranulation and NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating agents that show efficacy in older patients, did not compromise BI 836858-induced NK-cell-mediated ADCC. Evaluation of BI 836858-mediated ADCC in serial marrow AML aspirates in patients who received a 10-day course of DAC (pre-DAC, days 4, 11, and 28 post-DAC) revealed significantly higher ADCC in samples at day 28 post-DAC when compared with pre-DAC treatment. Analysis of ligands to activating receptors (NKG2D) showed significantly increased NKG2D ligand [NKG2DL] expression in day 28 post-DAC samples compared with pre-DAC samples; when NKG2DL receptor was blocked using antibodies, BI 836858-mediated ADCC was significantly decreased, suggesting that DAC enhances AML blast susceptibility to BI 836858 by upregulating NKG2DL. These data provide a rationale for combination therapy of Fc-engineered antibodies such as BI 836858 with azanucleosides in elderly patients with AML.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic Combined Chemotherapy ProtocolsAzacitidineCells, CulturedCombined Modality TherapyCytotoxicity, ImmunologicDecitabineDrug SynergismHL-60 CellsHumansImmunoglobulin Fc FragmentsKiller Cells, NaturalLeukemia, Myeloid, AcuteRecombinant ProteinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAzacitidineBI 836858CD33 protein, humanDecitabineImmunoglobulin Fc FragmentsRecombinant ProteinsSialic Acid Binding Ig-like Lectin 3

Identifiers

PMID27013443
PMCPMC4900955
OpenAlexW2417767096

What OpenQuestion holds

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Registered trials

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.