Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors
Open accessAbstract
CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells, indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment. In vivo, daratumumab was highly active and interrupted xenograft tumor growth at low dosing. Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms. These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.
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Daratumumab is a human IgGκ monoclonal antibody that targets CD38.
“Daratumumab, a human IgGκ monoclonal antibody that targets CD38, 8 has shown substantial single-agent efficacy and a manageable safety profile in phase 1-2 studies involving patients with heavily pretreated relapsed or refractory multiple myeloma, with reported overall response rates of 29% and 36%.9,10”
From Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. (2016) · cites this paper as [8]
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- Authors
- de Weers, M., Tai, Y.-T., van der Veer, M. S., Bakker, J. M., Vink, T., Jacobs, D. C. H., Oomen, L. A., Peipp, M., Valerius, T., Slootstra, J. W., Mutis, T., Bleeker, W. K., Anderson, K. C., Lokhorst, H. M., van de Winkel, J. G. J., & Parren, P. W. H. I.
- Affiliations
- Genmab , 3584 CM Utrecht ,
- Harvard University (US)
- Department of Clinical Chemistry and Hematology, University Medical Center , 3584 CX Utrecht ,
- Genmab (Netherlands) (NL)
- Christian-Albrechts-Universität zu Kiel (DE)
- Pepscan (Netherlands) (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Vink, Tom
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-01
- Volume
- 186
- Issue
- 3
- Pages
- 1840-1848
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2141502099
- Cited by
- 1,037
- References
- 53
- Citations by year
- 2026: 52 · 2025: 55 · 2024: 73 · 2023: 77 · 2022: 93 · 2021: 103 · 2020: 110 · 2019: 86 · 2018: 80 · 2017: 79 · 2016: 77 · 2015: 50 · 2014: 36 · 2013: 28 · 2012: 15
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- daratumumab, CD38, multiple myeloma, monoclonal antibodies, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, cytotoxicity mechanism, mesenchymal stem cells, xenograft tumor growth, hematologic malignancies, immunotherapy
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Antineoplastic Agents, Binding Sites, Antibody, Cricetulus, Cytotoxicity, Immunologic, Female, Cricetinae, Humans, Membrane Glycoproteins, Mice, Transgenic, Molecular Sequence Data, Multiple Myeloma, CHO Cells, Mice, SCID, Hematologic Neoplasms, Xenograft Model Antitumor Assays, NIH 3T3 Cells, Cell Line, Tumor, Mice, ADP-ribosyl Cyclase 1, HEK293 Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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