Evidence map›Paper›PMID 31981494›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

An Optimized Full-Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-leukemia Activity and Reversible Hematological Toxicity.

Yik Andy Yeung, Veena Krishnamoorthy, Danielle Dettling, Cesar Sommer, Kris Poulsen, Irene Ni, Amber Pham, Wei Chen, Sindy Liao-Chan, Kevin Lindquist and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 41 citations in OpenAlex.

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  14. Immune therapy: a new therapy for acute myeloid leukemia.Blood science (Baltimore, Md.) · 2023
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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

16 authors at 1 institution in 1 country.

Yik Andy YeungCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA. Electronic address: yeungyik@yahoo.com.
Veena KrishnamoorthyCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Danielle DettlingCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Cesar SommerCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Kris PoulsenCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Irene NiCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Amber PhamCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Wei ChenCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Sindy Liao-ChanCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Kevin LindquistCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
S Michael ChinCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Allison Given ChunykBiomedicine Design, Pfizer Inc., San Diego, CA 94080, USA.
Wenyue HuDrug Safety R&D, Pfizer Inc., San Diego, CA 94080, USA.
Barbra SasuCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA.
Javier Chaparro-RiggersCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA. Electronic address: javier.chaparro-riggers@pfizer.com.
Ivana DjureticCancer Immunology Discovery, Oncology R&D, Pfizer Inc., South San Francisco, CA 94080, USA. Electronic address: ivanadj@hotmail.com.
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

FLT3 (FMS-like tyrosine kinase 3), expressed on the surface of acute myeloid leukemia (AML) blasts, is a promising AML target, given its role in the development and progression of leukemia, and its limited expression in tissues outside the hematopoietic system. Small molecule FLT3 kinase inhibitors have been developed, but despite having clinical efficacy, they are effective only on a subset of patients and associated with high risk of relapse. A durable therapy that can target a wider population of AML patients is needed. Here, we developed an anti-FLT3-CD3 immunoglobulin G (IgG)-based bispecific antibody (7370) with a high affinity for FLT3 and a long half-life, to target FLT3-expressing AML blasts, irrespective of FLT3 mutational status. We demonstrated that 7370 has picomolar potency against AML cell lines in vitro and in vivo. 7370 was also capable of activating T cells from AML patients, redirecting their cytotoxic activity against autologous blasts at low effector-to-target (E:T) ratio. Additionally, under our dosing regimen, 7370 was well tolerated and exhibited potent efficacy in cynomolgus monkeys by inducing complete but reversible depletion of peripheral FLT3

Indexed as

AnimalsAntibodies, BispecificAntineoplastic Agents, ImmunologicalBone MarrowCD3 ComplexCell Line, TumorDisease Models, AnimalDose-Response Relationship, Drugfms-Like Tyrosine Kinase 3HematopoiesisHumansImmunoglobulin GImmunophenotypingLeukemia, Myeloid, AcuteLymphocyte DepletionMacaca fascicularisAntibodies, BispecificAntineoplastic Agents, ImmunologicalCD3 ComplexFLT3 protein, humanfms-Like Tyrosine Kinase 3Immunoglobulin Gacute myeloid leukemiabispecificCD3FLT3hematopoieticprogenitorT cell redirection

Identifiers

PMID31981494
PMCPMC7054815
OpenAlexW3000497625

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.