Daratumumab
Daratumumab Basic information
- Product Name:
- Daratumumab
- Synonyms:
-
- Daratumumab
- Daratumumab - 20mg/ml in water
- Daratumumab 21.7mg/ml
- Daratumumab USP/EP/BP
- Research Grade Daratumumab(DHD80801)
- Anti-Human CD38, Human Antibody,myeloma,inhibit,tumor,antibody,cell,adhesion,cytotoxicity,Inhibitor,Daratumumab
- Research Grade Daratumumab
- Daratumumab - 20mg/ml in buffer
- CAS:
- 945721-28-8
- MW:
- 0
- Mol File:
- Mol File
Daratumumab Chemical Properties
- form
- Liquid
- color
- Colorless to light yellow
- CAS DataBase Reference
- 945721-28-8
Daratumumab Usage And Synthesis
History
Daratumumab (trade name: Darzalex) is a revolutionary breakthrough in the treatment of multiple myeloma. It is a humanized anti-CD38 monoclonal antibody discovered and developed by the Danish biotechnology company Genmab, and subsequently licensed to Janssen Biotech for global commercialization in 2012. The drug has a unique mechanism of action, directly killing tumor cells by binding with high affinity to the CD38 glycoprotein highly expressed on the surface of multiple myeloma cells, activating multiple immune mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis (ADCP), while also possessing immunomodulatory effects. Based on its significant efficacy in monotherapy for patients with relapsed and refractory multiple myeloma, daratumumab received accelerated approval from the US FDA on November 16, 2015, becoming the first approved CD38-targeted drug. Subsequently, its indications expanded rapidly, especially based on pivotal phase III clinical trials such as the CASTOR (daratumumab in combination with bortezomib and dexamethasone) and POLLUX (daratumumab in combination with lenalidomide and dexamethasone) trials. These trials demonstrated that daratumumab in combination with standard therapy could significantly improve patients' progression-free survival, thus making it a cornerstone of first- and second-line treatment options for multiple myeloma.
Uses
Daratumumab (Anti-Human CD38) is the first-in-class human-specific anti-CD38 monoclonal antibody (IgG1). Daratumumab has anti-multiple myeloma (MM) effect. Daratumumab impairs MM cell adhesion, which results in an increased sensitivity of MM to proteasome inhibition[1][2].
Clinical Use
Human monoclonal IgG1κ antibody against CD38
antigen:
Treatment of multiple myeloma
in vivo
Daratumumab (i.p.; 0.5 mg/kg; 14 d after challenge with Daudi-luc cells) inhibits outgrowth of CD38-expressing tumor cells in mouse xenograft tumor models[2].
| Animal Model: | 8- to 10-wk-old C.B-17 SCID mice (luciferase-expressing Daudi cells)[2] |
| Dosage: | 0.5 mg/kg |
| Administration: | I.p.; 14 day after challenge with Daudi-luc cells |
| Result: | Effectively inhibited tumor growth compared with control-treated animals in which tumor grew rapidly and therefore required euthanasia on day 35. On day 28 and day 35, tumor size in Daratumumab-treated animals was significantly different from the control. |
Drug interactions
Potentially hazardous interactions with other drugs
Vaccines: avoid with live vaccines.
Metabolism
No data
References
[1] Ghose J, Viola D, et al. Daratumumab induces CD38 internalization and impairs myeloma cell adhesion. Oncoimmunology. 2018;7(10):e1486948. Published 2018 Jul 23. DOI:10.1080/2162402X.2018.1486948
[2] de Weers M, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840-1848. DOI:10.4049/jimmunol.1003032
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