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231224s2017 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2017.05.016
|2 doi
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|a pubmed25n0908.xml
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|a (NLM)28578024
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|a (PII)S1521-6616(16)30708-2
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Taylor, Ronald P
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Hexamerization-enhanced CD20 antibody mediates complement-dependent cytotoxicity in serum genetically deficient in C9
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|c 2017
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
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|2 rdacarrier
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|a Date Completed 28.08.2017
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|a Date Revised 10.12.2019
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2017 Elsevier Inc. All rights reserved.
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|a We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca2+ during CDC (as assessed with FLUO-4) that were extended in time. This suggests that small C5b-8 pores allow Ca2+ to enter the cell, while dissipation of the fluorescent signal accompanying cell disintegration is delayed. The Ca2+ signal is retained concomitantly with TOPRO-3 (viability dye) staining, thereby confirming that Ca2+ influx represents the most proximate mediator of cell death by CDC
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|a Journal Article
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|a Complement
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|a Immunotherapy
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|a Monoclonal antibodies
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|a Complement C9
|2 NLM
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|a Complement Membrane Attack Complex
|2 NLM
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|a complement C5b-8 complex
|2 NLM
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|a Rituximab
|2 NLM
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|a 4F4X42SYQ6
|2 NLM
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|a Complement System Proteins
|2 NLM
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|a 9007-36-7
|2 NLM
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|a Calcium
|2 NLM
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|a SY7Q814VUP
|2 NLM
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| 700 |
1 |
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|a Lindorfer, Margaret A
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cook, Erika M
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Beurskens, Frank J
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Schuurman, Janine
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Parren, Paul W H I
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zent, Clive S
|e verfasserin
|4 aut
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| 700 |
1 |
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|a VanDerMeid, Karl R
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Burack, Richard
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mizuno, Masashi
|e verfasserin
|4 aut
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| 700 |
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|a Morgan, B Paul
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 181(2017) vom: 30. Aug., Seite 24-28
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnas
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| 773 |
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|g volume:181
|g year:2017
|g day:30
|g month:08
|g pages:24-28
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|u http://dx.doi.org/10.1016/j.clim.2017.05.016
|3 Volltext
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