ArticleBritish journal of haematology2018
Targeting CD38 with daratumumab is lethal to Waldenström macroglobulinaemia cells.
Article in British journal of haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Multicenter phase 2 study of daratumumab monotherapy in patients with previously treated Waldenström macroglobulinemia.Blood advances · 2020Trial
- Multifunctional CD38 in the pathogenesis and treatment of B-cell lymphomas.American journal of blood research · 2026Review
- Novel Approaches to Managing Patients with Relapsed and Refractory Waldenström Macroglobulinemia.Current hematologic malignancy reports · 2024Review
- Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.Clinical & translational immunology · 2024Article
- AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.Cancers · 2023Article
- The Circular Life of Human CD38: From Basic Science to Clinics and Back.Molecules (Basel, Switzerland) · 2020Review
- Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses.Blood advances · 2020Article
- Flow cytometric evaluation of CD38 expression levels in the newly diagnosed T-cell acute lymphoblastic leukemia and the effect of chemotherapy on its expression in measurable residual disease, refractory disease and relapsed disease: an implication for anti-CD38 immunotherapy.Journal for immunotherapy of cancer · 2020Article
- Review
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
CD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti-CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells. In vitro Dara treatment of WM cells (including ibrutinib-resistant lines) elicited antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cell phagocytosis (ADCP) and direct apoptosis. In vivo, Dara treatment was well tolerated and delayed tumour growth in RPCI-WM1-xenografted mice. CD38 is reported to augment B-cell receptor (BCR) signalling; we noted that Dara significantly attenuated phosphorylated SYK, LYN, BTK, PLCγ2, ERK1/2, AKT, mTOR, and S6 levels, and this effect was augmented by cotreatment with ibrutinib. Indeed, WM cells, including ibrutinib-resistant WM cell lines treated with the ibrutinib + Dara combination, showed significantly more cell death through ADCC, CDC, ADCP and apoptosis relative to single-agent Dara or ibrutinib. In summary, we are the first to report the in vitro and in vivo anti-WM activity of Dara. Furthermore, we show a close connection between BCR and CD38 signalling, which can be co-targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.
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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.