ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Growth and activation of natural killer cells ex vivo from children with neuroblastoma for adoptive cell therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 104 citations in OpenAlex.
- Trial
- Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.Current oncology reports · 2026Review
- Optimal genetic feeder cell-expanded and engineered NK cell products are composed of CD56Cancer immunology, immunotherapy : CII · 2026Article
- Purification and antibody-free ex-vivo expansion of peripheral blood-derived autologous natural killer cells: A Malaysian case series on patient safety and tolerability.SAGE open medical case reports · 2026Article
- Genetically engineered K562 cells augment NK cell cytotoxicity against acute myeloid leukemia and reduce dependency on IL-15.Medical oncology (Northwood, London, England) · 2025Article
- Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives.Cancer metastasis reviews · 2024Review
- Phase I study of safety and efficacy of allogeneic natural killer cell therapy in relapsed/refractory neuroblastomas post autologous hematopoietic stem cell transplantation.Scientific reports · 2024Article
- Artificial antigen-presenting cells: the booster for the obtaining of functional adoptive cells.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- CTLs heterogeneity and plasticity: implications for cancer immunotherapy.Molecular cancer · 2024Review
- Development of Innate-Immune-Cell-Based Immunotherapy for Adult T-Cell Leukemia-Lymphoma.Cells · 2024Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Phenotypic and functional characterisation of locally produced natural killer cells ex vivo expanded with the K562-41BBL-mbIL21 cell line.Clinical and experimental medicine · 2023Article
- Process engineering of natural killer cell-based immunotherapy.Trends in biotechnology · 2023Review
- Evaluation of allogeneic and autologous membrane-bound IL-21-expanded NK cells for chronic lymphocytic leukemia therapy.Blood advances · 2022Article
- Antitumor and Immunomodulatory Properties of the Bulgarian Endemic PlantPlants (Basel, Switzerland) · 2022Article
- T cells, particularly activated CD4Cancer immunology, immunotherapy : CII · 2022Article
- Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma.Oncoimmunology · 2022Article
- Dissecting the cellular components ofOncoimmunology · 2022Article
- Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2Journal for immunotherapy of cancer · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeAdoptive transfer of natural killer (NK) cells combined with tumor-specific monoclonal antibodies (mAb) has therapeutic potential for malignancies. We determined if large numbers of activated NK (aNK) cells can be grown ex vivo from peripheral blood mononuclear cells (PBMC) of children with high-risk neuroblastoma using artificial antigen-presenting cells (aAPC). EXPERIMENTAL
designIrradiated K562-derived Clone 9.mbIL21 aAPC were cocultured with PBMC, and propagated NK cells were characterized with flow cytometry, cytotoxicity assays, Luminex multicytokine assays, and a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of disseminated neuroblastoma.
resultsCoculturing patient PBMC with aAPC for 14 days induced 2,363- ± 443-fold expansion of CD56(+)CD3(-)CD14(-) NK cells with 83% ± 3% purity (n = 10). Results were similar to PBMC from normal donors (n = 5). Expression of DNAM-1, NKG2D, FcγRIII/CD16, and CD56 increased 6- ± 3-, 10- ± 2-, 21- ± 20-, and 18- ± 3-fold, respectively, on day 14 compared with day 0, showing activation of NK cells. In vitro, aNK cells were highly cytotoxic against neuroblastoma cell lines and killing was enhanced with GD2-specific mAb ch14.18. When mediating cytotoxicity with ch14.18, release of TNF-α, granulocyte macrophage colony-stimulating factor, IFN-γ, sCD40L, CCL2/MCP-1, CXCL9/MIG, and CXCL11/I-TAC by aNK cells increased 4-, 5-, 6-, 15-, 265-, 917-, and 363-fold (151-9,121 pg/mL), respectively, compared with aNK cells alone. Survival of NOD/SCID mice bearing disseminated neuroblastoma improved when treated with thawed and immediately intravenously infused cryopreserved aNK cells compared with untreated mice and was further improved when ch14.18 was added.
conclusionPropagation of large numbers of aNK cells that maintain potent antineuroblastoma activities when cryopreserved supports clinical testing of adoptive cell therapy with ch14.18.
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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.