ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement-Limiting Conditions.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Selection of laboratory assays for reliable assessment of complement-dependent cytotoxicity: impact of assay choice on CDC quantification.Frontiers in immunology · 2026Article
- Targeting CD20 for B-cell Depletion in Autoimmune Kidney Disease: Next Generation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Complement activation by IgG subclasses is governed by their ability to oligomerize upon antigen binding.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6.Molecular cancer therapeutics · 2024Article
- Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.Cell death & disease · 2023Article
- Therapeutic targeting of TRAIL death receptors.Biochemical Society transactions · 2023Review
- The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation.Clinical & translational immunology · 2023Article
- Deceiving and escaping complement - the evasive journey of the malaria parasite.Trends in parasitology · 2022Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- Internalization of HIV-1 by Phagocytes Is Increased When Virions Are Opsonized with Multimeric Antibody in the Presence of Complement.Journal of virology · 2022Article
- IgG subclass and Fc glycosylation shifts are linked to the transition from pre- to inflammatory autoimmune conditions.Frontiers in immunology · 2022Review
- mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine.Frontiers in immunology · 2022Article
- On-target IgG hexamerisation driven by a C-terminal IgM tail-piece fusion variant confers augmented complement activation.Communications biology · 2021Article
- Development of Therapeutic Antibodies and Modulating the Characteristics of Therapeutic Antibodies to Maximize the Therapeutic Efficacy.Biotechnology and bioprocess engineering : BBE · 2021Review
- The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs.Antibodies (Basel, Switzerland) · 2020Review
- Complement System: Promoter or Suppressor of Cancer Progression?Antibodies (Basel, Switzerland) · 2020Review
- How Do mAbs Make Use of Complement to Kill Cancer Cells? The Role of CaAntibodies (Basel, Switzerland) · 2020Review
- Design and characterization of novel dual Fc antibody with enhanced avidity for Fc receptors.Proteins · 2020Article
- Antibody-mediated complement activation in pathology and protection.Immunology and cell biology · 2020Review
- A universal reporter cell line for bioactivity evaluation of engineered cytokine products.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, we demonstrated that IgG Abs can organize into ordered hexamers after binding their cognate Ags expressed on cell surfaces. This process is dependent on Fc:Fc interactions, which promote C1q binding, the first step in classical pathway complement activation. We went on to engineer point mutations that stimulated IgG hexamer formation and complement-dependent cytotoxicity (CDC). The hexamer formation-enhanced (HexaBody) CD20 and CD38 mAbs support faster, more robust CDC than their wild-type counterparts. To further investigate the CDC potential of these mAbs, we used flow cytometry, high-resolution digital imaging, and four-color confocal microscopy to examine their activity against B cell lines and primary chronic lymphocytic leukemia cells in sera depleted of single complement components. We also examined the CDC activity of alemtuzumab (anti-CD52) and mAb W6/32 (anti-HLA), which bind at high density to cells and promote substantial complement activation. Although we observed little CDC for mAb-opsonized cells reacted with sera depleted of early complement components, we were surprised to discover that the Hexabody mAbs, as well as ALM and W6/32, were all quite effective at promoting CDC in sera depleted of individual complement components C6 to C9. However, neutralization studies conducted with an anti-C9 mAb verified that C9 is required for CDC activity against cell lines. These highly effective complement-activating mAbs efficiently focus activated complement components on the cell, including C3b and C9, and promote CDC with a very low threshold of MAC binding, thus providing additional insight into their enhanced efficacy in promoting CDC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.