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Cited by 333Multiple Myeloma Research and TreatmentsMonoclonal and Polyclonal Antibodies ResearchLymphoma Diagnosis and Treatment

The DOI matches its Crossref record; 49 of the 54 references it cites were found in a registry or an index.

SAR650984, A Novel Humanized CD38-Targeting Antibody, Demonstrates Potent Antitumor Activity in Models of Multiple Myeloma and Other CD38+ Hematologic Malignancies

Deckert, Jutta, Wetzel, Marie-Cécile, Bartle, Laura M., Skaletskaya, Anna, Goldmacher, Victor S., Vallée, François, Zhou-Liu, Qing, Ferrari, Paul, Pouzieux, Stéphanie, Lahoute, Charlotte, Dumontet, Charles, Plesa, Adriana, Chiron, Marielle, Lejeune, Pascale, Chittenden, Thomas, Park, Peter U., Blanc, Véronique·2014·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-14-0695

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Abstract

Purpose: The CD38 cell surface antigen is expressed in diverse hematologic malignancies including multiple myeloma, B-cell non-Hodgkin lymphoma (NHL), B-cell chronic lymphocytic leukemia, B-cell acute lymphoblastic leukemia (ALL), and T-cell ALL. Here, we assessed the antitumor activity of the anti-CD38 antibody SAR650984. Experimental Design: Activity of SAR650984 was examined on lymphoma, leukemia and multiple myeloma cell lines, primary multiple myeloma samples, and multiple myeloma xenograft models in immunodeficient mice. Results: We identified a humanized anti-CD38 antibody with strong proapoptotic activity independent of cross-linking agents, and potent effector functions including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis (ADCP), equivalent in vitro to rituximab in CD20+ and CD38+ models. This unique antibody, termed SAR650984, inhibited the ADP-ribosyl cyclase activity of CD38, likely through an allosteric antagonism as suggested by 3D structure analysis of the complex. In vivo, SAR650984 was active in diverse NHL, ALL, and multiple myeloma CD38+ tumor xenograft models. SAR650984 demonstrated single-agent activity comparable with rituximab or cyclophosphamide in Daudi or SU-DHL-8 lymphoma xenograft models with induction of the proapoptotic marker cleaved capase-7. In addition, SAR650984 had more potent antitumor activity than bortezomib in NCI-H929 and Molp-8 multiple myeloma xenograft studies. Consistent with its mode of action, SAR650984 demonstrated potent proapoptotic activity against CD38+ human primary multiple myeloma cells. Conclusion: These results validate CD38 as a therapeutic target and support the current evaluation of this unique CD38-targeting functional antibody in phase I clinical trials in patients with CD38+ B-cell malignancies. Clin Cancer Res; 20(17); 4574–83. ©2014 AACR.

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Crossref · 10.1158/1078-0432.ccr-14-0695

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Metadata

Authors
Deckert, J., Wetzel, M.-C., Bartle, L. M., Skaletskaya, A., Goldmacher, V. S., Vallée, F., Zhou-Liu, Q., Ferrari, P., Pouzieux, S., Lahoute, C., Dumontet, C., Plesa, A., Chiron, M., Lejeune, P., Chittenden, T., Park, P. U., & Blanc, V.
Affiliations
  • ImmunoGen (United States) (US)
  • Sanofi (France) (FR)
  • Centre National de la Recherche Scientifique (FR)
  • 5Hematology Laboratory, Hospices Civils de Lyon, Pierre Bénite, France and CRCL, INSERM 1052-CNRS 5286, Lyon, France.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2014-09-01
Volume
20
Issue
17
Pages
4574-4583
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-14-0695
OpenAlex
W2072259475
Cited by
333
References
54
Citations by year
2026: 17 · 2025: 23 · 2024: 22 · 2023: 25 · 2022: 48 · 2021: 48 · 2020: 36 · 2019: 25 · 2018: 22 · 2017: 20 · 2016: 24 · 2015: 21 · 2014: 2
FWCI
15.84
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
anti-CD38 monoclonal antibody, CD38, multiple myeloma, B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, allosteric antagonism, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, rituximab, xenograft models, apoptosis
MeSH terms
Rituximab, Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Humans, Membrane Glycoproteins, Multiple Myeloma, Lymphoma, B-Cell, Hematologic Neoplasms, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, ADP-ribosyl Cyclase 1, Antibodies, Monoclonal, Murine-Derived, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions

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