ArticleCancer immunology, immunotherapy : CII2018
Daratumumab augments alloreactive natural killer cell cytotoxicity towards CD38+ multiple myeloma cell lines in a biochemical context mimicking tumour microenvironment conditions.
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 32 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Daratumumab provides a survival benefit in relapsed and refractory Multiple Myeloma, independent of baseline clinical characteristics: A meta-analysis.Pharmacology research & perspectives · 2021Pooled it
- Navigating the Therapeutic Landscape of Multiple Myeloma: Immunotherapy, Microenvironment, and Resistance.Biomedicines · 2026Review
- CD38+ NK cells: novel players in immunoregulation.Frontiers in immunology · 2026Review
- Mechanism by which SAHA regulates HLA-E expression via the endoplasmic reticulum stress-related PERK/ATF4/CHOP pathway in neuroblastoma.Frontiers in immunology · 2026Article
- Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell linesFrontiers in immunology · 2024Article
- Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.Frontiers in cell and developmental biology · 2024Review
- Exploring the potential of combining IL-2-activated NK cells with an anti-PDL1 monoclonal antibody to target multiple myeloma-associated macrophages.Cancer immunology, immunotherapy : CII · 2023Article
- Expanded natural killer cells potentiate the antimyeloma activity of daratumumab, lenalidomide, and dexamethasone in a myeloma xenograft model.Cancer immunology, immunotherapy : CII · 2023Article
- Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.Signal transduction and targeted therapy · 2023Review
- Antibody-dependent cellular cytotoxicity-inducing antibodies enhance the natural killer cell anti-cancer response against patient-derived pancreatic cancer organoids.Frontiers in immunology · 2023Article
- A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma.Future oncology (London, England) · 2023Article
- Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.Cancer immunology, immunotherapy : CII · 2022Article
- Review
- Regulation of CD38 on Multiple Myeloma and NK Cells by Monoclonal Antibodies.International journal of biological sciences · 2022Review
- Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML.International journal of molecular sciences · 2021Article
- Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma.Cancer science · 2021Review
- Article
- Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma.Cancers · 2021Article
- Activated Natural Killer Cells Withstand the Relatively Low Glucose Concentrations Found in the Bone Marrow of Multiple Myeloma Patients.Frontiers in oncology · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Hypoxia, lactate, prostaglandin E2 (PGE2) or combinations were selected to mimic the TME. To investigate this, NK cells from healthy donors were isolated and NK cell ADCC capacity in response to MM cells was assessed in flow cytometry-based cytotoxicity and degranulation (CD107a) assays in the presence of TME factors. Hypoxia, lactate and PGE2 reduced cytotoxicity of NK cells against myeloma target cells. The addition of daratumumab (anti-CD38 antibody) augmented NK-cell cytotoxicity against target cells expressing high CD38, but not against CD38 low or negative target cells also in the presence of TME. Co-staining for inhibitory KIRs and NKG2A demonstrated that daratumumab enhanced degranulation of all NK cell subsets. Nevertheless, KIR-ligand mismatched NK cells were slightly better effector cells than KIR-ligand matched NK cells. In summary, our study shows that combination therapy using strategies to maximize activating NK cell signaling by triggering ADCC in combination with an approach to minimize inhibitory signaling through a selection of KIR-ligand mismatched donors, can help to overcome the NK-suppressive TME. This can serve as a platform to improve the clinical efficacy of NK cells.
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.