ArticleScientific reports2016
Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Trimerization of CD40L-specific affibody molecules using collagen domains enhances target binding and CD40 blockade.Cellular and molecular life sciences : CMLS · 2026Article
- GPA33-Targeted Trimeric Immunotoxin Exhibits Enhanced Antitumor Activity in Human Colorectal Cancer Xenografts.International journal of molecular sciences · 2026Article
- Advances in Nanobody-Based Platforms for Precision Cancer Diagnosis and Therapy.Polymer science & technology (Washington, D.C.) · 2025Review
- Engineering Decavalent, Sperm-Binding Laminin-IgG Hybrid Antibodies for Potent Non-Hormonal Contraception.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.International journal of molecular sciences · 2024Review
- Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.Antibodies (Basel, Switzerland) · 2024Article
- Multi-targeted immunotherapeutics to treat B cell malignancies.Journal of controlled release : official journal of the Controlled Release Society · 2023Review
- A PD-L1/EGFR bispecific antibody combines immune checkpoint blockade and direct anti-cancer action for an enhanced anti-tumor response.Oncoimmunology · 2023Article
- Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies.The EMBO journal · 2021Article
- Review
- A Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor.The AAPS journal · 2020Article
- On-target restoration of a split T cell-engaging antibody for precision immunotherapy.Nature communications · 2019Article
- Article
- A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts.Scientific reports · 2019Article
- Carcinoembryonic Antigen (CEA)-Specific 4-1BB-Costimulation Induced by CEA-Targeted 4-1BB-Agonistic Trimerbodies.Frontiers in immunology · 2019Article
- A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity.Nature communications · 2018Article
- Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies.Cancer immunology, immunotherapy : CII · 2018Article
- Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment.Frontiers in immunology · 2018Review
- Article
- Review
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIE(XVIII)) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIE(XVIII) trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIE(XVIII) modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas.
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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.