Evidence map›Paper›PMID 40624796›Full record

ArticlemAbs2025

Development and preclinical characterization of AMG 329: a human antibody neutralizing FLT3 ligand.

Annie Lau-Kilby, Michele Gunsior, Agata Bartczak, Susan Chyou, James Hester, Dorothy Sims, Xiaodong Xiao, Peter Pavlik, Yan Chen, Kerry A Casey and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Annie Lau-KilbyResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Michele GunsiorResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Agata BartczakResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Susan ChyouResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
James HesterResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Dorothy SimsResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
Xiaodong XiaoResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
Peter PavlikResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
Yan ChenResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
Kerry A CaseyResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
Kamelia ZerroukiResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Qian WangResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
M Jack BorrokResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.
Anna M HansenResearch and Protein Engineering, AstraZeneca, Gaithersburg, MD, USA.
William A ReesResearch and Translational Sciences, Horizon Therapeutics, PLC, Rockville, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) signaling pathway regulates the development and activity of dendritic cells (DCs) and other myeloid cells, including monocytes. FLT3L, DCs, and monocytes have been implicated in several autoimmune diseases. Here, we describe the development and characterization of a human immunoglobulin G1λ monoclonal antibody (AMG 329; formerly MEDI1116/VIB-1116/HZN-1116) targeting human FLT3L. AMG 329 was derived from a large human combined antibody display library; it was optimized to enhance affinity for FLT3L and reduce antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. Binding affinity was determined by surface plasmon resonance interaction analysis. Specificity of FLT3L was measured using cell-based flow cytometry and an in vitro functional neutralization assay. ADCC activity was measured using an in vitro cell culture system. Toxicity and toxicokinetics were evaluated in cynomolgus monkeys during AMG 329 dosing (5-100 mg/kg; ≤ 27 weeks) and recovery (≤32 weeks). The AMG 329 antigen-binding region selectively bound to human and cynomolgus monkey FLT3L with affinities of 170 and 63 pM, respectively. AMG 329 specifically bound to and neutralized soluble and cell-bound human FLT3L and did not induce ADCC. AMG 329 administration generally reduced circulating plasmacytoid, conventional DC, and classical monocyte relative proportions in cynomolgus monkeys in a non-dose-dependent manner. Disruption of the FLT3/FLT3L signaling pathway presents a new potential therapeutic approach to treat autoimmune and inflammatory diseases. AMG 329 is a selective human monoclonal antibody antagonist of FLT3L that is currently being investigated in clinical studies.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingMembrane ProteinsAnimalsAntibody-Dependent Cell CytotoxicityHumansMacaca fascicularisMiceAntibodies, MonoclonalAntibodies, Neutralizingflt3 ligand proteinMembrane ProteinsAMG 329dendritic cellsFLT3FLT3 ligandmonocytesplasmacytoid dendritic cells

Identifiers

PMID40624796
PMCPMC12239813

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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.