ArticleCancers2018
Impact of HACA on Immunomodulation and Treatment Toxicity Following ch14.18/CHO Long-Term Infusion with Interleukin-2: Results from a SIOPEN Phase 2 Trial.
Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Efficacy and Safety of Anti-GD2 Immunotherapy with Dinutuximab Beta in the Treatment of Relapsed/Refractory High-Risk Neuroblastoma.Targeted oncology · 2025Pooled it
- Efficacy of anti-GD2 antibody immunotherapy with filgrastim and teceleukin versus standard treatment with sargramostim, aldesleukin and isotretinoin in children with high-risk neuroblastoma.International journal of clinical oncology · 2026Trial
- Fcγ Receptor Polymorphism in Patients with Relapsed/Refractory High-Risk Neuroblastoma Correlates with Outcomes in the SIOPEN Dinutuximab Beta Long-Term Infusion Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study.British journal of cancer · 2023Trial
- Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment.Frontiers in immunology · 2021Trial
- Tumor Microenvironment in Neuroblastoma and Immunotherapeutic Approaches: Towards More Effective Treatment.Cancers · 2026Review
- Affinity Affects the Functional Potency of Anti-GD2 Antibodies by Target-Mediated Drug Disposition.Cancers · 2025Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Recent Evidence-Based Clinical Guide for the Use of Dinutuximab Beta in Pediatric Patients with Neuroblastoma.Targeted oncology · 2023Review
- Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Anti-disialoganglioside antibody internalization by neuroblastoma cells as a mechanism of immunotherapy resistance.Cancer immunology, immunotherapy : CII · 2022Article
- Review
- Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy.Biologics : targets & therapy · 2019Review
- The Promise of Anti-idiotype Revisited.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 10 institutions in 7 countries.
Funding
Abstract
GD₂-directed immunotherapies improve survival of high-risk neuroblastoma (NB) patients (pts). Treatment with chimeric anti-GD₂ antibodies (Ab), such as ch14.18, can induce development of human anti-chimeric Ab (HACA). Here, we report HACA effects on ch14.18/CHO pharmacokinetics, pharmacodynamics and pain intensity in pts treated by long-term infusion (LTI) of ch14.18/CHO combined with IL-2. 124 pts received up to 5 cycles of ch14.18/CHO 10 days (d) infusion (10 mg/m²/d; d8⁻18) combined with s.c. IL-2 (6 × 10⁶ IU/m²/d; d1⁻5, d8⁻12). HACA, treatment toxicity, ch14.18/CHO levels, Ab-dependent cellular- (ADCC) and complement-dependent cytotoxicity (CDC) were assessed using respective validated assays. HACA-negative pts showed a steadily decreased pain in cycle 1 (74% pts without morphine by d5 of LTI) with further decrease in subsequent cycles. Ch14.18/CHO peak concentrations of 11.26 ± 0.50 µg/mL found in cycle 1 were further elevated in subsequent cycles and resulted in robust GD₂-specific CDC and ADCC. Development of HACA (21% of pts) resulted in strong reduction of ch14.18/CHO levels, abrogated CDC and ADCC. Surprisingly, no difference in pain toxicity between HACA-positive and -negative pts was found. In conclusion, ch14.18/CHO LTI combined with IL-2 results in strong activation of Ab effector functions. Importantly, HACA response abrogated CDC but did not affect pain intensity indicating CDC-independent pain induction.
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