Evidence map›Paper›PMID 24311721›Full record

ArticleBlood2014

Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML.

George S Laszlo, Chelsea J Gudgeon, Kimberly H Harrington, Justine Dell'Aringa, Kathryn J Newhall, Gary D Means, Angus M Sinclair, Roman Kischel, Stanley R Frankel, Roland B Walter

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
13.0field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.

  1. Pooled it
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  6. Strategic innovations: Tackling challenges of immunotherapy in acute myeloid leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
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34 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

10 authors at 3 institutions in 2 countries.

George S LaszloClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Chelsea J Gudgeon
Kimberly H Harrington
Justine Dell'Aringa
Kathryn J Newhall
Gary D Means
Angus M Sinclair
Roman Kischel
Stanley R Frankel
Roland B Walter
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 CA015704NCI NIH HHS P30-CA015704-35S6
6 · The paper itself

Abstract

CD33 is a valid target for acute myeloid leukemia (AML) but has proven challenging for antibody-drug conjugates. Herein, we investigated the cellular determinants for the activity of the novel CD33/CD3-directed bispecific T-cell engager antibody, AMG 330. In the presence of T cells, AMG 330 was highly active against human AML cell lines and primary AML cells in a dose- and effector to target cell ratio-dependent manner. Using cell lines engineered to express wild-type CD33 at increased levels, we found a quantitative relationship between AMG 330 cytotoxicity and CD33 expression; in contrast, AMG 330 cytotoxicity was neither affected by common CD33 single nucleotide polymorphisms nor expression of the adenosine triphosphate-binding cassette (ABC) transporter proteins, P-glycoprotein or breast cancer resistance protein. Unlike bivalent CD33 antibodies, AMG 330 did not reduce surface CD33 expression. The epigenetic modifier drugs, panobinostat and azacitidine, increased CD33 expression in some cell lines and augmented AMG 330-induced cytotoxicity. These findings demonstrate that AMG 330 has potent CD33-dependent cytolytic activity in vitro, which can be further enhanced with other clinically available therapeutics. As it neither modulates CD33 expression nor is affected by ABC transporter activity, AMG 330 is highly promising for clinical exploration as it may overcome some limitations of previous CD33-targeted agents.

Indexed as

Gene Expression Regulation, LeukemicAC133 AntigenAntibodiesAntibodies, BispecificAntigens, CDAzacitidineCD3 ComplexCell Line, TumorEnzyme InhibitorsEpigenesis, GeneticGlycoproteinsHL-60 CellsHumansHydroxamic AcidsIndolesLeukemia, Myeloid, AcuteAC133 AntigenAMG 330AntibodiesAntibodies, BispecificAntigens, CDAzacitidineCD3 ComplexEnzyme InhibitorsGlycoproteinsHydroxamic AcidsIndolesO(6)-Methylguanine-DNA MethyltransferasePanobinostatPeptidesSialic Acid Binding Ig-like Lectin 3

Identifiers

PMID24311721
PMCPMC3901068
OpenAlexW2066915867

What OpenQuestion holds

Textmetadata
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.