ArticleCancer immunology, immunotherapy : CII2018
The role of interleukin-2, all-trans retinoic acid, and natural killer cells: surveillance mechanisms in anti-GD2 antibody therapy in neuroblastoma.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial.Journal for immunotherapy of cancer · 2020Trial
- ENPP3 CAR T cells combined with CD206 modulation suppress adrenocortical carcinoma.Journal for immunotherapy of cancer · 2026Article
- Immune Modulation Through KIR-HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer.International journal of molecular sciences · 2025Article
- Inhibitory receptors for HLA class I as immune checkpoints for natural killer cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2023Review
- Introduction to the Complexity of Cell Surface and Tissue Matrix Glycoconjugates.Advances in neurobiology · 2023Article
- Breaking down the tumor immune infiltration within pediatric sarcomas.Frontiers in endocrinology · 2023Review
- Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma.Journal for immunotherapy of cancer · 2023Article
- Neuroblastoma: When differentiation goes awry.Neuron · 2022Review
- Anti-GD2 Antibodies Conjugated to IL15 and IL21 Mediate Potent Antitumor Cytotoxicity against Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- The cyclin dependent kinase inhibitor p21Frontiers in oncology · 2022Article
- Next-generation humanized patient-derived xenograft mouse model for pre-clinical antibody studies in neuroblastoma.Cancer immunology, immunotherapy : CII · 2021Article
- Monoclonal Antibody Therapies for High Risk Neuroblastoma.Biologics : targets & therapy · 2021Review
- Patients' NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing.Cancer immunology, immunotherapy : CII · 2020Article
- Gangliosides and Neuroblastomas.International journal of molecular sciences · 2020Review
- Interleukin-15 Enhances Anti-GD2 Antibody-Mediated Cytotoxicity in an Orthotopic PDX Model of Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Engineering the TGFβ Receptor to Enhance the Therapeutic Potential of Natural Killer Cells as an Immunotherapy for Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Innate Immune Cells: A Potential and Promising Cell Population for Treating Osteosarcoma.Frontiers in immunology · 2019Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy. Nevertheless, these mechanisms are not fully understood. We developed a quantitative assay to test ADCC induced by the anti-GD2 antibody Hu14.18K322A in nine neuroblastoma cell lines and dissociated cells from orthotopic patient-derived xenografts (O-PDXs) in culture. IL-2 improved ADCC against neuroblastoma cells, and differentiation with all-trans retinoic acid stabilized GD2 expression on tumor cells and enhanced ADCC as well. Degranulation was highest in licensed NK cells that expressed CD158b (P < 0.001) and harbored a killer-cell immunoglobulin-like receptor (KIR) mismatch against the tumor-specific human leukocyte antigen (HLA; P = 0.016). In conclusion, IL-2 is an important component of immunotherapy because it can improve the cytolytic function of NK cells against neuroblastoma cells and could lower the antibody dose required for efficacy, thereby reducing toxicity. The effect of IL-2 may vary among individuals and a biomarker would be useful to predict ADCC following IL-2 activation. Sub-populations of NK cells may have different levels of activity dependent on their licensing status, KIR expression, and HLA-KIR interaction. Better understanding of HLA-KIR interactions and the molecular changes following retinoid-induced differentiation is necessary to delineate their role in ADCC.
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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.