Daratumumab binds to mobilized CD34+ cells of myeloma patients in vitro without cytotoxicity or impaired progenitor cell growth
Background The monoclonal antibody daratumumab, approved for treating myeloma, targets CD38, a protein on myeloma and also on CD34+ hematopoietic progenitor cells. Because mobilized CD34+ cells are critical for stem cell transplant, we investigated the in vitro activity of daratumumab on mobilized CD34+ cells from myeloma patients with no prior exposure to daratumumab. Methods We determined the number of CD38 molecules per CD34+ cell, and whether daratumumab bound to CD34+ cells, whether C1q bound to daratumumab-coated CD34+ cells and whether daratumumab-related complement-dependent cytotoxicity (CDC) occurred. We also examined CD34+ cell progenitor cell colony capacity in assays with pre-plating incubation of CD34+ cells with daratumumab alone or with daratumumab and the CD59 inhibitory antibody BRIC229, and also assessed CD34+ cell responses to increasing doses of daratumumab in caspase 3/7 activity assays. Results Although 75% of mobilized CD34+ cells co-express CD38, CD38 was minimally present on CD34+ cells compared to Daudi and KG-1 controls, C1q did not bind to daratumumab-coated CD34+ cells, and CDC did not occur. CD34+ cells incubated in complement-rich human serum with daratumumab alone or with daratumumab and BRIC229, and then plated in progenitor cell assays, produced similar numbers of colonies as controls. In progenitor cell assays with cryopreserved or fresh unselected or CD34-selected cells, daratumumab did not affect progenitor cell capacity, and in caspase 3/7 activity assays CD34+ cells were not affected by increasing doses of daratumumab. Conclusion In vitro, daratumumab is not toxic to mobilized CD34+ progenitor cells from myeloma patients..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Experimental hematology & oncology - 7(2018), 1 vom: 16. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Xun [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| Anmerkungen: |
© The Author(s) 2018 |
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| doi: |
10.1186/s40164-018-0119-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC210442240X |
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| 520 | |a Background The monoclonal antibody daratumumab, approved for treating myeloma, targets CD38, a protein on myeloma and also on CD34+ hematopoietic progenitor cells. Because mobilized CD34+ cells are critical for stem cell transplant, we investigated the in vitro activity of daratumumab on mobilized CD34+ cells from myeloma patients with no prior exposure to daratumumab. Methods We determined the number of CD38 molecules per CD34+ cell, and whether daratumumab bound to CD34+ cells, whether C1q bound to daratumumab-coated CD34+ cells and whether daratumumab-related complement-dependent cytotoxicity (CDC) occurred. We also examined CD34+ cell progenitor cell colony capacity in assays with pre-plating incubation of CD34+ cells with daratumumab alone or with daratumumab and the CD59 inhibitory antibody BRIC229, and also assessed CD34+ cell responses to increasing doses of daratumumab in caspase 3/7 activity assays. Results Although 75% of mobilized CD34+ cells co-express CD38, CD38 was minimally present on CD34+ cells compared to Daudi and KG-1 controls, C1q did not bind to daratumumab-coated CD34+ cells, and CDC did not occur. CD34+ cells incubated in complement-rich human serum with daratumumab alone or with daratumumab and BRIC229, and then plated in progenitor cell assays, produced similar numbers of colonies as controls. In progenitor cell assays with cryopreserved or fresh unselected or CD34-selected cells, daratumumab did not affect progenitor cell capacity, and in caspase 3/7 activity assays CD34+ cells were not affected by increasing doses of daratumumab. Conclusion In vitro, daratumumab is not toxic to mobilized CD34+ progenitor cells from myeloma patients. | ||
| 650 | 4 | |a Myeloma | |
| 650 | 4 | |a Daratumumab | |
| 650 | 4 | |a CD34+ | |
| 650 | 4 | |a Progenitor cells | |
| 700 | 1 | |a Wong, Sandy W. |4 aut | |
| 700 | 1 | |a Zhou, Ping |4 aut | |
| 700 | 1 | |a Chaulagain, Chakra P. |4 aut | |
| 700 | 1 | |a Doshi, Parul |4 aut | |
| 700 | 1 | |a Klein, Andreas K. |4 aut | |
| 700 | 1 | |a Sprague, Kellie |4 aut | |
| 700 | 1 | |a Kugelmass, Adin |4 aut | |
| 700 | 1 | |a Toskic, Denis |4 aut | |
| 700 | 1 | |a Warner, Melissa |4 aut | |
| 700 | 1 | |a Miller, Kenneth B. |4 aut | |
| 700 | 1 | |a Lee, Lisa |4 aut | |
| 700 | 1 | |a Varga, Cindy |4 aut | |
| 700 | 1 | |a Comenzo, Raymond L. |0 (orcid)0000-0002-6255-5824 |4 aut | |
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