Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors
| Autor: | Wim K. Bleeker, Matthias Peipp, Joost M. Bakker, Jan G. J. van de Winkel, Michel de Weers, Michael S. van der Veer, Kenneth C. Anderson, Paul W. H. I. Parren, Thomas Valerius, Yu-Tzu Tai, Jerry W. Slootstra, Tom Vink, Lukas A. Oomen, Tuna Mutis, Daniëlle C H Jacobs, Henk M. Lokhorst |
|---|---|
| Přispěvatelé: | Medical oncology laboratory, Hematology laboratory, Hematology |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cytotoxicity
Immunologic Stromal cell medicine.medical_treatment Immunology Molecular Sequence Data Antineoplastic Agents Mice Transgenic CHO Cells Mice SCID Biology Mice Cricetulus Cell Line Tumor Cricetinae medicine Immunology and Allergy Cytotoxic T cell Animals Humans Amino Acid Sequence Isatuximab Membrane Glycoproteins SLAMF7 Antibody-Dependent Cell Cytotoxicity Daratumumab Antibodies Monoclonal Immunotherapy ADP-ribosyl Cyclase 1 Xenograft Model Antitumor Assays Complement-dependent cytotoxicity medicine.anatomical_structure HEK293 Cells Hematologic Neoplasms Cancer research NIH 3T3 Cells Female Bone marrow Binding Sites Antibody Multiple Myeloma |
| Zdroj: | 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 2011, ' Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors ', Journal of Immunology, vol. 186, no. 3, pp. 1840-1848 . https://doi.org/10.4049/jimmunol.1003032 Journal of Immunology, 186(3), 1840-1848. American Association of Immunologists |
| ISSN: | 0022-1767 |
| DOI: | 10.4049/jimmunol.1003032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|