Evidence map›Paper›PMID 26305211›Full record

ArticlePloS one2015

The Broad Anti-AML Activity of the CD33/CD3 BiTE Antibody Construct, AMG 330, Is Impacted by Disease Stage and Risk.

Kimberly H Harrington, Chelsea J Gudgeon, George S Laszlo, Kathryn J Newhall, Angus M Sinclair, Stanley R Frankel, Roman Kischel, Guang Chen, Roland B Walter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.1field-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.

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

31 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
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  5. Recent advances in CAR-T cell therapy for acute myeloid leukaemia.Journal of cellular and molecular medicine · 2024
    Review
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  16. An Update on Immune Based Therapies in Acute Myeloid Leukemia: 2021 and Beyond!Advances in experimental medicine and biology · 2021
    Article
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  18. Review
  19. Article
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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

9 authors at 3 institutions in 2 countries.

Kimberly H HarringtonClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Chelsea J GudgeonClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
George S LaszloClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Kathryn J NewhallAmgen, Inc., Seattle, Washington, United States of America.
Angus M SinclairAmgen, Inc., Thousand Oaks, California, United States of America.
Stanley R FrankelAmgen, Inc., Rockville, Maryland, United States of America.
Roman KischelAmgen Research (Munich) GmbH, Munich, Germany.
Guang ChenAmgen, Inc., Seattle, Washington, United States of America.
Roland B WalterClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Medicine, Division of Hematology, University of Washington, Seattle, Washington, United States of America; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
Amgen (United States) · USFred Hutch Cancer Center · USAmgen (Germany) · DE

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
NCI NIH HHS P30 CA015704
6 · The paper itself

Abstract

The CD33/CD3-bispecific T-cell engaging (BiTE) antibody construct, AMG 330, potently lyses CD33+ leukemic cells in vitro. Using specimens from 41 patients with acute myeloid leukemia (AML), we studied the factors that might contribute to clinical response or resistance. For this purpose, thawed aliquots of primary AML samples were immunophenotypically characterized and subjected to various doses of AMG 330 in the presence or absence of healthy donor T-cells. After 48 hours, drug-specific cytotoxicity was quantified and correlated with CD33 expression levels, amounts of T-cells present, and other disease characteristics. AMG 330 caused modest cytotoxicity that was correlated with the amount of autologous T-cells (P = 0.0001) but not CD33 expression, as AMG 330 exerted marked cytotoxic effects in several specimens with minimal CD33 expression. With healthy donor T-cells added, AMG 330 cytotoxicity depended on the drug dose and effector:target (E:T) cell ratio. High cytotoxic activity was observed even with minimal CD33 expression, and AMG 330 cytotoxicity and CD33 expression correlated only at high E:T cell ratio and high AMG 330 doses (P<0.003). AMG 330 resulted in significantly higher cytotoxicity in specimens from patients with newly diagnosed AML than those with relapsed/refractory disease despite similar levels of CD33 on myeloblasts. AMG 330 cytotoxicity also appeared greater in specimens from patients with favorable-risk disease as compared to other specimens. Together, our data demonstrate that AMG 330 is highly active in primary AML specimens across the entire disease spectrum, while suggesting the presence of yet undefined, CD33-independent, relative resistance mechanisms in specific patient subsets.

Indexed as

AdultAgedAged, 80 and overAntibodies, BispecificCD3 ComplexCytotoxicity, ImmunologicFemaleGene Expression Regulation, LeukemicHumansImmunophenotypingLeukemia, Myeloid, AcuteMaleMiddle AgedSialic Acid Binding Ig-like Lectin 3T-LymphocytesAMG 330Antibodies, BispecificCD3 ComplexSialic Acid Binding Ig-like Lectin 3

Identifiers

PMID26305211
PMCPMC4549148
OpenAlexW2210801850

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.