ArticleJournal for immunotherapy of cancer2023
IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 19 citations in OpenAlex.
- Why antibody isotype matters for immunotherapy.Antibody therapeutics · 2026Review
- Article
- Fc-engineering for improved cancer immunotherapy.Biochemical Society transactions · 2026Review
- Retargeted adenoviruses for local IgA and CD47 blocker production as a novel cancer therapy.EMBO molecular medicine · 2026Article
- Review
- Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.Advances in experimental medicine and biology · 2026Review
- Virtual screening and MD simulation-guided discovery of CDK12-IN-3, a potent ALK inhibitor suppressing neuroblastoma growthFrontiers in chemistry · 2026Article
- Hybrid IgE-IgG1 antibodies (IgEG): a new antibody class that combines IgE and IgG functionality.mAbs · 2025Article
- Article
- High-plex imaging of hepatoblastoma and adjacent liver in pediatric patients reveals a predominant myeloid infiltrate expressing immune-checkpoints.Cancer immunology, immunotherapy : CII · 2025Article
- The Efficacy of Targeted Monoclonal IgA Antibodies Against Pancreatic Ductal Adenocarcinoma.Cells · 2025Article
- Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life.PNAS nexus · 2025Article
- Unraveling the dual roles of tumor-infiltrating antibodies in solid tumors: friend or foe in the tumor microenvironment?Frontiers in immunology · 2025Review
- The relevance of tumor target expression levels on IgA-mediated cytotoxicity in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Glycosylation: mechanisms, biological functions and clinical implications.Signal transduction and targeted therapy · 2024Review
- Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade.Journal for immunotherapy of cancer · 2024Article
- Evaluation of a Combinatorial Immunotherapy Regimen That Can Cure Mice Bearing MYCN-Driven High-Risk Neuroblastoma That Resists Current Clinical Therapy.Journal of clinical medicine · 2024Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Prospects of anti-GD2 immunotherapy for retinoblastoma.Frontiers in immunology · 2024Review
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunotherapy targeting GD2 is very effective against high-risk neuroblastoma, though administration of anti-GD2 antibodies induces severe and dose-limiting neuropathic pain by binding GD2-expressing sensory neurons. Previously, the IgG1 ch14.18 (dinutuximab) antibody was reformatted into the IgA1 isotype, which abolishes neuropathic pain and induces efficient neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) via activation of the Fc alpha receptor (FcαRI/CD89).
methodsTo generate an antibody suitable for clinical application, we engineered an IgA molecule (named IgA3.0 ch14.18) with increased stability, mutated glycosylation sites and substituted free (reactive) cysteines. The following mutations were introduced: N45.2G and P124R (CH1 domain), C92S, N120T, I121L and T122S (CH2 domain) and a deletion of the tail piece P131-Y148 (CH3 domain). IgA3.0 ch14.18 was evaluated in binding assays and in ADCC and antibody-dependent cellular phagocytosis (ADCP) assays with human, neuroblastoma patient and non-human primate effector cells. We performed mass spectrometry analysis of
resultsADCC and ADCP assays showed that particularly neutrophils and macrophages from healthy donors, non-human primates and patients with neuroblastoma are able to kill neuroblastoma tumor cells efficiently with IgA3.0 ch14.18. IgA3.0 ch14.18 contains a more favorable glycosylation pattern, corresponding to an increased antibody half-life in mice compared with IgA1 and IgA2. Furthermore, IgA3.0 ch14.18 penetrates neuroblastoma tumors in vivo and halts tumor outgrowth in both 9464D-GD2 and IMR32 long-term tumor models.
conclusionsIgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.