ArticleJournal for immunotherapy of cancer2025
Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03294954 (GD2 Specific Chimeric Antigen Receptor), which is not on this map. Cited by 15 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.
GD2 Specific Chimeric Antigen Receptor (CAR) and Interleukin-15 Expressing Autologous Natural Killer T-cells to Treat Children With Neuroblastoma
Who cites it
15 citing papers in PubMed.
- Exploring CAR cell therapies beyond CAR-T for myeloid malignancies.Journal of biomedical science · 2026Review
- Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.Current oncology reports · 2026Review
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Innate-like T Cell Biology in the Tumor Microenvironment Implications for Cancer Immunotherapy.Cells · 2026Review
- CD4Nature medicine · 2026Article
- Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Redefining cell therapy: CAR-engineered innate immune cells to conquer solid and hematologic malignancies.Molecular biology reports · 2026Review
- Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.Biology · 2025Review
- Facts and Hopes of Chimeric Antigen Receptor-Redirected NK T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Response to: Correspondence on "Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15" by Ataca Atilla and Atilla.Journal for immunotherapy of cancer · 2025Article
- Modulating TNFα Activity to Address Cytokine Related Toxicity.Journal for immunotherapy of cancer · 2025Article
- Frontiers of cytokine engineering in CAR cell therapy for cancer.Frontiers in oncology · 2025Review
- CAR-iNKT cells: redefining the frontiers of cellular immunotherapy.Frontiers in immunology · 2025Review
- CAR-iNKT cells for cancer therapy: a comprehensive review of engineering, mechanisms, and clinical progress.ImmunotherapyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells (PBMCs). 12 previously treated patients on DLs 1 through 4 did not experience significant toxicity. Our root-cause analysis revealed no genetic alterations of known clinical significance and excluded the possibility of clonal expansion due to insertional retroviral mutagenesis. We report that the use of aAPCs instead of PBMCs for CAR-NKT restimulation contributed to a hyperproliferative state associated with distinct gene expression that possibly led to explosive lymphocyte expansion and uncontrolled toxicity in the patient. These findings warrant the implementation of measures to control immune cell activation during manufacture of cell therapy products, especially those armed with transgenic cytokines.
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.