ArticleBlood advances2021
FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Daratumumab in high-risk MGUS and low-risk smoldering myeloma: results of the Phase II D-PRISM study.Nature communications · 2026Trial
- Review
- Review
- Review
- Memory-like NK cell differentiation, inhibitory NKG2A blockade, and improved recognition via antibody or CAR engineering combine to enhance NK cell attack against multiple myeloma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.Annals of hematology · 2024Article
- Review
- Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells.MedComm · 2024Article
- Functional multiomics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma.Blood neoplasia · 2024Article
- Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma.Journal for immunotherapy of cancer · 2024Article
- A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?Frontiers in immunology · 2024Review
- Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.Frontiers in cell and developmental biology · 2024Review
- Recent advances in cellular immunotherapy for lymphoid malignancies.Blood research · 2023Review
- Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering.Nature communications · 2023Article
- Phenotypic and functional analysis in HER2+ targeted therapy of human NK cell subpopulation according to the expression of FcεRIγ and NKG2C in breast cancer patients.Cancer immunology, immunotherapy : CII · 2023Article
- NK Cell Phenotype Is Associated With Response and Resistance to Daratumumab in Relapsed/Refractory Multiple Myeloma.HemaSphere · 2023Article
- Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance.International journal of molecular sciences · 2022Review
- Review
- Adaptive single-KIRJournal for immunotherapy of cancer · 2022Article
- Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Monoclonal antibodies (mAbs) are a central component of therapy for hematologic malignancies. Widely used mAb agents in multiple myeloma (MM) include daratumumab and elotuzumab. However, not all patients respond to these agents, and resistance is a significant clinical issue. A recently discovered subset of human natural killer (NK) cells lacking expression of FcεRIγ (g-NK cells) was found to have a multifold increase in antibody-dependent effector functions after CD16 crosslinking. In this study, we tested the capacity of g-NK cells to enhance the efficacy of therapeutic mAbs against MM. In vitro, we found that g-NK cells have strikingly superior anti-myeloma cytotoxicity compared with conventional NK (cNK) cells when combined with daratumumab or elotuzumab (∼sixfold; P < .001). In addition, g-NK cells naturally expressed minimal surface CD38 and SLAMF7, which reduced the incidence of therapeutic fratricide. In tumor-naïve murine models, the persistence of g-NK cells in blood and spleen was >10 times higher than that of cNK cells over 31 days (P < .001). In vivo efficacy studies showed that the combination of daratumumab and g-NK cells led to a >99.9% tumor reduction (by flow cytometry analysis) compared with the combination of daratumumab and cNK cells (P < .001). Moreover, treatment with daratumumab and g-NK cells led to complete elimination of myeloma burden in 5 of 7 mice. Collectively, these results underscore the unique ability of g-NK cells to potentiate the activity of therapeutic mAbs and overcome limitations of current off-the-shelf NK cell therapies without the need for cellular irradiation or genetic engineering.
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Registered trials
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