ArticlePharmaceuticals (Basel, Switzerland)2021
Exatecan Antibody Drug Conjugates Based on a Hydrophilic Polysarcosine Drug-Linker Platform.
Article in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- From Payload-First Toward Dual-Mechanism Antibody-Drug Conjugates.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- NPTXR as a novel therapeutic target: efficacy of antibody-drug conjugates in preclinical tumor models.Cancer cell international · 2026Article
- Antibody-Drug Conjugates Targeting HER2 and Trop-2: A New Force in Precision Treatment for Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Exatecan Payload-Based Antibody-Drug Conjugates with a Short Hydrophilic Cleavable Linker.ACS medicinal chemistry letters · 2026Article
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Development of tCAP(N3): Affinity Peptide-Aided, pH-Triggered Strategy for Site-Specific Native IgG Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Expanding the payload scope in antibody-drug conjugates by delivery of hydroxy-containing drugs through self-immolative phosphoramidates.Nature communications · 2026Article
- Legumain-Cleavable Top1i Antibody-Drug Conjugates without Self-Immolative Spacers Demonstrate Potent Antitumor Activity.Journal of medicinal chemistry · 2025Article
- Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).RSC advances · 2025Review
- Development of Optimized Exatecan-Based Immunoconjugates with Potent Antitumor Efficacy in HER2-Positive Breast Cancer.Journal of medicinal chemistry · 2025Article
- OBI-992, a Novel TROP2-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models.Molecular cancer therapeutics · 2025Article
- Technical, preclinical, and clinical developments of Fc-glycan-specific antibody-drug conjugates.RSC medicinal chemistry · 2025Review
- Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.Frontiers in pharmacology · 2025Review
- Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- Rational Identification of Novel Antibody-Drug Conjugate with High Bystander Killing Effect against Heterogeneous Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Review
- Design and Evaluation of Phosphonamidate-Linked Exatecan Constructs for Highly Loaded, Stable, and Efficacious Antibody-Drug Conjugates.Molecular cancer therapeutics · 2024Article
- Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release.Chemical science · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We herein report the development and evaluation of a novel HER2-targeting antibody-drug conjugate (ADC) based on the topoisomerase I inhibitor payload exatecan, using our hydrophilic monodisperse polysarcosine (PSAR) drug-linker platform (PSARlink). In vitro and in vivo experiments were conducted in breast and gastric cancer models to characterize this original ADC and gain insight about the drug-linker structure-activity relationship. The inclusion of the PSAR hydrophobicity masking entity efficiently reduced the overall hydrophobicity of the conjugate and yielded an ADC sharing the same pharmacokinetic profile as the unconjugated antibody despite the high drug-load of the camptothecin-derived payload (drug-antibody ratio of 8). Tra-Exa-PSAR10 demonstrated strong anti-tumor activity at 1 mg/kg in an NCI-N87 xenograft model, outperforming the FDA-approved ADC DS-8201a (Enhertu), while being well tolerated in mice at a dose of 100 mg/kg. In vitro experiments showed that this exatecan-based ADC demonstrated higher bystander killing effect than DS-8201a and overcame resistance to T-DM1 (Kadcyla) in preclinical HER2+ breast and esophageal models, suggesting potential activity in heterogeneous and resistant tumors. In summary, the polysarcosine-based hydrophobicity masking approach allowsfor the generation of highly conjugated exatecan-based ADCs having excellent physicochemical properties, an improved pharmacokinetic profile, and potent in vivo anti-tumor activity.
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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.