ArticleProceedings of the National Academy of Sciences of the United States of America2014
A general approach to site-specific antibody drug conjugates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 312 citations in OpenAlex.
- ACE-Breast-02: a randomized phase III trial of ARX788 versus lapatinib plus capecitabine for HER2-positive advanced breast cancer.Signal transduction and targeted therapy · 2025Trial
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- ADC Conjugation Strategies: From Technological Evolution to a Practical Selection Framework.Pharmaceutics · 2026Review
- Antibody-Drug Conjugates (ADCs): A Review of Structural Design, Technological Evolution, and Future Perspectives.Molecules (Basel, Switzerland) · 2026Review
- Efficient Preparation of Homogenous Antibody Conjugates via Glycosite-Specific Transglycosylation Enabled by Readily Available Glycosyl Donors.Angewandte Chemie (International ed. in English) · 2026Article
- Unnatural Amino Acid and Emerging Chemistry Approaches to Map RNA-Protein Interactions.Angewandte Chemie (International ed. in English) · 2026Review
- Nanobody-Based Drug Delivery: Emerging Strategies for Targeted Cancer Therapy.International journal of nanomedicine · 2026Review
- High throughput screening of eukaryotic release factor 1 variants to enhance noncanonical amino acid incorporation.bioRxiv : the preprint server for biology · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- A review of conjugation technologies for antibody drug conjugates.Antibody therapeutics · 2025Review
- Strategies to Expand the Genetic Code of Mammalian Cells.Chemical reviews · 2025Review
- Determination of the decapping efficiency of THIOMAB™ antibodies with the engineered cysteine in the Fc region for making antibody-drug conjugates by specific hinge fragmentation-liquid chromatography.Analytical and bioanalytical chemistry · 2025Article
- Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody-Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Recent advances in the expanding genetic code.Current opinion in chemical biology · 2024Review
- Reaching New Heights in Genetic Code Manipulation with High Throughput Screening.Chemical reviews · 2024Review
- Generation of binder-format-payload conjugate-matrices by antibody chain-exchange.Nature communications · 2024Article
- Synthesis at the Interface of Chemistry and Biology.Accounts of chemical research · 2024Review
- Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion.Chemical reviews · 2024Review
- Directed Evolution of a Bacterial Leucyl tRNA in Mammalian Cells for Enhanced Noncanonical Amino Acid Mutagenesis.ACS synthetic biology · 2024Article
- Applications of genetic code expansion technology in eukaryotes.Protein & cell · 2024Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues. The advantages of the oxime-bonded, site-specific NDCs were even more apparent when low-antigen-expressing (2+) target cell lines were used in the comparative studies. NDCs generated with protease-cleavable linkers demonstrated that the site of conjugation had a significant impact on the stability of these rationally designed prodrug linkers. In a single-dose rat toxicology study, a site-specific anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments support the notion that chemically defined antibody conjugates can be synthesized in commercially relevant yields and can lead to antibody drug conjugates with improved properties relative to the heterogeneous conjugates formed by nonspecific chemical modification.
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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.