ArticleBlood2020
CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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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.
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Who cites it
88 citing papers in PubMed, 124 citations in OpenAlex.
- Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma.Blood advances · 2021Trial
- Allo-defensive, multiplex base-edited, anti-CD38 CAR T cells for 'off-the-shelf' immunotherapy.Haematologica · 2026Article
- Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.Molecular therapy. Advances · 2026Article
- Depletion of the RNA-Editing Enzyme ADAR1 Invigorates the Antitumor Immunity of NK Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dual-functioning Targeted ADAM17 Blocker CD16 (TAB16) mediates selective ADAM17 inhibition in NK cells and engages overexpressed ADAM17 in tumor cells to induce cytotoxicity.Frontiers in immunology · 2026Article
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Metabolomic Investigation of Myelodysplastic Syndromes, Multiple Myeloma, and Homozygous β-Thalassemia.Cells · 2025Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Site-specific genome engineering of primary human natural killer cells for programmable anti-tumor function.bioRxiv : the preprint server for biology · 2025Article
- A phase 2 study of Daratumumab with Thalidomide and dexamethasone in relapsed and/or Refractory Myeloma (RRMM).Blood cancer journal · 2025Article
- Multiple myeloma with 1q gain/amplification exhibits reduced CD38 expression via interleukin-6 receptor overexpression.British journal of haematology · 2025Article
- Engineering innate immune cells for cancer immunotherapy.Nature biotechnology · 2025Review
- The clinical landscape of CAR NK cells.Experimental hematology & oncology · 2025Review
- 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
- Research Progress of NK Cells in Glioblastoma Treatment.OncoTargets and therapy · 2025Review
- CD38-CAR human NK cells in combination with ATRA enhance cytotoxicity against CD38-expressing hematologic malignancies.Blood neoplasia · 2024Article
- Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities.Experimental hematology & oncology · 2024Review
- [The advancement of cuproptosis in hematological tumors].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.
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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.