ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Targeting CD38 Enhances the Antileukemic Activity of Ibrutinib in Chronic Lymphocytic Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- A phase II study of daratumumab and ibrutinib for relapsed/refractory chronic lymphocytic leukemia.Blood cancer journal · 2026Article
- Multifunctional CD38 in the pathogenesis and treatment of B-cell lymphomas.American journal of blood research · 2026Review
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- Impact of Protein Kinase C Activation and Monoclonal Antibodies on Immune Checkpoint Regulation and B Cell Function in Patients with Chronic Lymphocytic Leukemia.Biomedicines · 2025Article
- CD38 prognostic role in chronic lymphocytic leukemia patients treated with standard chemotherapy or targeted agents: a monocentric real-life experience.Frontiers in oncology · 2025Article
- CD38 regulates chronic lymphocytic leukemia proliferation via CD45 phosphatase activity.Molecular therapy. Oncology · 2024Article
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Human serum albumin-based drug-free macromolecular therapeutics induce apoptosis in chronic lymphocytic leukemia patient cells by crosslinking of CD20 and/or CD38 receptors.Drug delivery and translational research · 2024Article
- Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.Clinical & translational immunology · 2024Article
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- Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?Cancers · 2022Review
- Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment.Cancer cell international · 2022Review
- The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.American journal of physiology. Cell physiology · 2022Review
- CD38 in the age of COVID-19: a medical perspective.Physiological reviews · 2021Review
- CD38: A Potential Therapeutic Target in Cardiovascular Disease.Cardiovascular drugs and therapy · 2021Review
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- CD38 Deficiency Ameliorates Chronic Graft-Frontiers in immunology · 2021Article
- NAD-Linked Metabolism and Intervention in Short Telomere Syndromes and Murine Models of Telomere Dysfunction.Frontiers in aging · 2021Review
- The Extracellular NADome Modulates Immune Responses.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeCD38 has emerged as a high-impact therapeutic target in multiple myeloma, with the approval of daratumumab (anti-CD38 mAb). The clinical importance of CD38 in patients with chronic lymphocytic leukemia (CLL) has been known for over 2 decades, although it's relevance as a therapeutic target in CLL remains understudied. EXPERIMENTAL
designWe investigated the biological effects and antitumor mechanisms engaged by daratumumab in primary CLL cells. Besides its known immune-effector mechanisms (antibody-dependent cell-mediated cytotoxicity, complement-dependent death, and antibody-dependent cellular phagocytosis), we also measured direct apoptotic effects of daratumumab alone or in combination with ibrutinib.
resultsIn addition to immune-effector mechanisms; daratumumab also induced direct apoptosis of primary CLL cells, which was partially dependent on FcγR cross-linking. For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCγ2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib. In comparison to single-agent treatment, the combination of ibrutinib and daratumumab resulted in significantly enhanced anti-CLL activity
conclusionsOverall, our data demonstrate the antitumor mechanisms of daratumumab in CLL; furthermore, we show how cotargeting BTK and CD38 lead to a robust anti-CLL effect, which has clinical implications.
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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.