ArticleBioconjugate chemistry2023
Generation of DAR1 Antibody-Drug Conjugates for Ultrapotent Payloads Using Tailored GlycoConnect Technology.
Article in Bioconjugate chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Generation of DAR1 Glycosite-Specific Antibody-Drug Conjugates Using DisacLink Technology.Chembiochem : a European journal of chemical biology · 2026Article
- ADC Conjugation Strategies: From Technological Evolution to a Practical Selection Framework.Pharmaceutics · 2026Review
- Enabling the synthesis of multi-payload thio-antibody conjugates through the use of pyridazinediones,RSC chemical biology · 2026Article
- Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies.Beilstein journal of organic chemistry · 2026Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Biocompatible Chemistry: A Plug-and-Play Toolbox for Chemical Biology Research.Chembiochem : a European journal of chemical biology · 2025Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Methods for the Generation of Single-Payload Antibody-Drug Conjugates.ChemMedChem · 2025Article
- Emerging Claudin18.2-targeting Therapy for Systemic Treatment of Gastric Cancer: Seeking Nobility Amidst Danger.Anti-cancer agents in medicinal chemistry · 2025Review
- Antibody-drug conjugates in cancer therapy: current advances and prospects for breakthroughs.Frontiers in cell and developmental biology · 2025Review
- Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Click Chemistry for Biofunctional Polymers: From Observing to Steering Cell Behavior.Chemical reviews · 2024Review
- Modular Semisynthetic Approach to Generate T Cell-Dependent Bispecific Constructs from Recombinant IgG1 Antibodies.Bioconjugate chemistry · 2024Article
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Rapid Access to Potent Bispecific T Cell Engagers Using Biogenic Tyrosine Click Chemistry.Bioconjugate chemistry · 2023Article
- Disulfide re-bridging reagents for single-payload antibody-drug conjugates.Chemical communications (Cambridge, England) · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
GlycoConnect technology can be readily adapted to provide different drug-to-antibody ratios (DARs) and is currently also evaluated in various clinical programs, including ADCT-601 (DAR2), MRG004a (DAR4), and XMT-1660 (DAR6). While antibody-drug conjugates (ADCs) typically feature a DAR2-8, it has become clear that ADCs with ultrapotent payloads (e.g., PBD dimers and calicheamicin) can only be administered to patients at low doses (<0.5 mg/kg), which may compromise effective biodistribution and may be insufficient to reach target receptor saturation in the tumor. Here, we show that GlycoConnect technology can be readily extended to DAR1 ADCs without the need of antibody re-engineering. We demonstrate that various ultrapotent, cytotoxic payloads are amenable to this methodology. In a follow-up experiment, HCC-1954 tumor spheroids were treated with either an AlexaFluor647-labeled DAR1 or DAR2 PBD-based ADC to study the effect on tumor penetration. Significant improvement of tumor spheroid penetration was observed for the DAR1 ADC compared to the DAR2 ADC at an equal payload dose, underlining the potential of a lower DAR for ADCs bearing ultrapotent payloads.
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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.