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Bivalent binding on...
Bivalent binding on cells varies between anti-CD20 antibodies and is dose-dependent
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- Bondza, Sina (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- ten Broeke, Toine (författare)
- Univ Med Ctr Utrecht, Ctr Translat Immunol, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands.
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- Nestor, Marika, 1976- (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Leusen, Jeanette H. W. (författare)
- Univ Med Ctr Utrecht, Ctr Translat Immunol, Utrecht, Netherlands.
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- Buijs, Jos (författare)
- Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Ridgeview Instruments AB, Uppsala, Sweden.
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(creator_code:org_t)
- 2020-08-02
- 2020
- Engelska.
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Ingår i: mAbs. - : TAYLOR & FRANCIS INC. - 1942-0862 .- 1942-0870. ; 12:1
- Relaterad länk:
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https://www.tandfonl...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Based on their mechanism of action, two types of anti-CD20 antibodies are distinguished: Type I, which efficiently mediate complement-dependent cytotoxicity, and Type II, which instead are more efficient in inducing direct cell death. Several molecular characteristics of these antibodies have been suggested to underlie these different biological functions, one of these being the manner of binding to CD20 expressed on malignant B cells. However, the exact binding model on cells is unclear. In this study, the binding mechanism of the Type I therapeutic antibodies rituximab (RTX) and ofatumumab (OFA) and the Type II antibody obinutuzumab (OBI) were established by real-time interaction analysis on live cells. It was found that the degree of bivalent stabilization differed for the antibodies: OFA was stabilized the most, followed by RTX and then OBI, which had the least amount of bivalent stabilization. Bivalency inversely correlated with binding dynamics for the antibodies, with OBI displaying the most dynamic binding pattern, followed by RTX and OFA. For RTX and OBI, bivalency and binding dynamics were concentration dependent; at higher concentrations the interactions were more dynamic, whereas the percentage of antibodies that bound bivalent was less, resulting in concentration-dependent apparent affinities. This was barely noticeable for OFA, as almost all molecules bound bivalently at the tested concentrations. We conclude that the degree of bivalent binding positively correlates with the complement recruiting capacity of the investigated CD20 antibodies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Affinity
- binding kinetics
- CD20
- cell-based assay
- receptor-ligand interactions
- therapeutic antibodies
- rituximab
- ofatumumab
- obinutuzumab
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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