ArticlePLoS biology2016
A Novel Platform for the Potentiation of Therapeutic Antibodies Based on Antigen-Dependent Formation of IgG Hexamers at the Cell Surface.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 220 citations in OpenAlex.
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- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
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- Pharmacologic activity, safety, and preliminary efficacy of GEN3009, a CD37-targeting DuoHexaBody, in relapsed or refractory B-cell non-Hodgkin's lymphoma.Journal for immunotherapy of cancer · 2026Article
- Affinity Enhancement in Discrete Multivalent MegaMolecules.Chembiochem : a European journal of chemical biology · 2026Article
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- MtrE Loop2-specific multiple antigenic peptide vaccine and monoclonal antibody confer complement-dependent protection against Neisseria gonorrhoeae.NPJ vaccines · 2026Article
- Human FcRL5 is an Fc receptor that simultaneously engages two IgGs.Science advances · 2026Article
- Discovery and characterization of an anti-Frontiers in microbiology · 2026Article
- Combination of Fc-Protein Engineering Strategies: Design and Evaluation of Antibody Effector Functions.Methods in molecular biology (Clifton, N.J.) · 2026Article
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- CD38-specific nanobody-based bispecific antibody recruiters (BARs) redirect complement-dependent cytotoxicity toward multiple myeloma cells.Scientific reports · 2025Article
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 2025Article
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- Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL.Blood cancer journal · 2025Article
- Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IgG antibodies can organize into ordered hexamers on cell surfaces after binding their antigen. These hexamers bind the first component of complement C1 inducing complement-dependent target cell killing. Here, we translated this natural concept into a novel technology platform (HexaBody technology) for therapeutic antibody potentiation. We identified mutations that enhanced hexamer formation and complement activation by IgG1 antibodies against a range of targets on cells from hematological and solid tumor indications. IgG1 backbones with preferred mutations E345K or E430G conveyed a strong ability to induce conditional complement-dependent cytotoxicity (CDC) of cell lines and chronic lymphocytic leukemia (CLL) patient tumor cells, while retaining regular pharmacokinetics and biopharmaceutical developability. Both mutations potently enhanced CDC- and antibody-dependent cellular cytotoxicity (ADCC) of a type II CD20 antibody that was ineffective in complement activation, while retaining its ability to induce apoptosis. The identified IgG1 Fc backbones provide a novel platform for the generation of therapeutics with enhanced effector functions that only become activated upon binding to target cell-expressed antigen.
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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.