ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Rescue of impaired NK cell activity in hodgkin lymphoma with bispecific antibodies in vitro and in patients.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 108 citations in OpenAlex.
- A Phase II Study of Acimtamig (AFM13) in Patients with CD30-Positive, Relapsed, or Refractory Peripheral T-cell Lymphomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.Journal for immunotherapy of cancer · 2026Article
- Novel tetrameric bispecific KK-LC-1×CD16A-armed memory-like NK cells enhance antitumor efficacy in gastric cancer.Journal for immunotherapy of cancer · 2025Article
- The bispecific innate cell engager AFM28 eliminates CD123Nature communications · 2025Article
- Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial.Nature medicine · 2025Article
- Current Developments in NK Cell Engagers for Cancer Immunotherapy: Focus on CD16A and NKp46.Immune network · 2024Review
- Ex Vivo Expanded Cord Blood Natural Killer Cells Combined with Rituximab and High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B Cell Non-Hodgkin Lymphoma.Transplantation and cellular therapy · 2024Article
- Differentiating Hodgkin Lymphoma and Sarcoid Reaction in Subsequent FDG-PET/CT: A Case Report and Literature Review.World journal of nuclear medicine · 2023Article
- Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment.Frontiers in immunology · 2023Review
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- The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?Biomedicines · 2022Review
- Role of the ITAM-Bearing Receptors Expressed by Natural Killer Cells in Cancer.Frontiers in immunology · 2022Review
- Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling.Frontiers in oncology · 2022Review
- Reduced frequency of cytotoxic CD56Cancer immunology, immunotherapy : CII · 2022Article
- Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Review
- Secreted Ligands of the NK Cell Receptor NKp30: B7-H6 Is in Contrast to BAG6 Only Marginally Released via Extracellular Vesicles.International journal of molecular sciences · 2021Article
- Natural Killer Cell Phenotype and Functionality Affected by Exposure to Extracellular Survivin and Lymphoma-Derived Exosomes.International journal of molecular sciences · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells represent a key component of the innate immune system against cancer. Nevertheless, malignant diseases arise in immunocompetent individuals despite tumor immunosurveillance. Hodgkin lymphoma (HL) is characterized by CD30(+) tumor cells and a massive infiltration of immune effector cells in affected lymph nodes. The latter obviously fail to eliminate the malignant cell population. Here, we tested for functional NK cell defects in HL and suggest an improvement of NK function by therapeutic means. We demonstrate that peripheral NK cells (pNK) from patients with HL fail to eliminate HL cell lines in ex vivo killing assays. Impaired NK cell function correlated with elevated serum levels of soluble ligands for NK cell receptors NKp30 (BAG6/BAT3) and NKG2D (MICA), factors known to constrict NK cell function. In vitro, NK cell cytotoxicity could be restored by an NKG2D/NKp30-independent bispecific antibody construct (CD30xCD16A). It artificially links the tumor receptor CD30 with the cytotoxicity NK cell receptor CD16A. Moreover, we observed that NK cells from patients treated with this construct were generally activated and displayed a restored cytotoxicity against HL target cells. These data suggest that reversible suppression of NK cell activity contributes to immune evasion in HL and can be antagonized therapeutically.
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