Evidence map›Paper›PMID 40805207›Full record

ArticleCancers2025

Affinity Affects the Functional Potency of Anti-GD2 Antibodies by Target-Mediated Drug Disposition.

Sascha Troschke-Meurer, Maxi Zumpe, Peter Moritz Ahrenberg, Torsten Ebeling, Nikolai Siebert, Piotr Grabarczyk, Holger N Lode

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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

7 authors.

Sascha Troschke-MeurerDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0000-0002-6185-462X
Maxi ZumpeDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0000-0003-0297-6739
Peter Moritz AhrenbergDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0009-0008-3689-708X
Torsten EbelingDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.
Nikolai SiebertDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0000-0001-6254-1302
Piotr GrabarczykClinic for Internal Medicine C-Hematology, Oncology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0000-0001-9270-7983
Holger N LodeDepartment of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475 Greifswald, Germany.ORCID 0000-0002-1201-208X

Funding

Deutsche Forschungsgemeinschaft Grant SI 2147/4Hector Stiftungen Grant M2116Recordati Rare Diseases N.A.
6 · The paper itself

Abstract

BACKGROUND/

objectivesHigh-risk neuroblastoma patients are treated with approved anti-ganglioside GD2 antibodies of moderate (dinutuximab beta; DB) and higher binding affinity (naxitamab; NAXI). We evaluated the functional potency of DB compared to NAXI and investigated the target-mediated drug disposition (TMDD).

methodsTumor spheroids were generated from neuroblastoma cells with varying GD2 expression, stably expressing iRFP680 as a viability marker. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were assessed in a long-term life-cell viability assay using serial dilutions of the GD2 antibodies. Binding activity was determined by flow cytometry. Processes involved in TMDD were analyzed, including antibody binding to dead tumor cells and to soluble GD2 (sGD2), antibody internalization into tumor and immune cells and the impact of sGD2 on DB and NAXI-mediated ADCC.

resultsDB and NAXI mediated a concentration-dependent ADCC response against GD2-positive spheroids and no response against GD2-negative spheroids. DB showed a significantly higher ADCC potency than NAXI in all GD2-positive spheroid models. Binding activity of DB and NAXI was not significantly different. However, the decrease of anti-GD2 antibody binding to viable GD2-positive tumor cells following co-incubation with dead GD2-positive tumor cells or sGD2 was significantly higher for NAXI than DB. Additionally, we found an increased internalization of NAXI compared to DB by tumor cells and particularly CD64+ monocytes. Finally, sGD2 impaired NAXI-mediated ADCC to a significantly greater extent than DB-mediated ADCC.

conclusionsDB has a higher ADCC potency over NAXI at clinically relevant concentrations, attributed to stronger TMDD effects of NAXI compared to DB.

Indexed as

antibody binding affinitydinutuximab betaGD2-based immunotherapynaxitamabneuroblastomatarget-mediated drug disposition

Identifiers

PMID40805207
PMCPMC12345752

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.