ArticleMolecular cancer therapeutics2015
Antibody Format and Drug Release Rate Determine the Therapeutic Activity of Noninternalizing Antibody-Drug Conjugates.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Quantitative Mass Spectrometry-Based Biodistribution of Monoclonal Antibodies: An Alternative to Radio-Biodistribution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GD2-Targeted Minibody-Drug Conjugates Match the Potency of IgG-Based ADCs in a Mouse Cancer Model.International journal of molecular sciences · 2026Article
- Targeting oncofetal fibronectin and neuropilin-1 in solid tumors with PL2 peptide.Scientific reports · 2025Article
- Structure-Activity Relationship of Antibody-Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody-Phosphorodiamidate Morpholino Oligomer Conjugates for Drug Development.Journal of medicinal chemistry · 2024Article
- Review
- Prospect of Gum Arabic-Cocoliposome Matrix to Encapsulate Curcumin for Oral Administration.Polymers · 2024Article
- Rabbit derived VL single-domains as promising scaffolds to generate antibody-drug conjugates.Scientific reports · 2023Article
- Minibody-Based and scFv-Based Antibody Fragment-Drug Conjugates Selectively Eliminate GD2-Positive Tumor Cells.International journal of molecular sciences · 2023Article
- Intra-Domain Cysteines (IDC), a New Strategy for the Development of Original Antibody Fragment-Drug Conjugates (FDCs).Pharmaceutics · 2022Article
- Research Progress of Conjugated Nanomedicine for Cancer Treatment.Pharmaceutics · 2022Review
- In Vitro Evaluation of Curcumin Encapsulation in Gum Arabic Dispersions under Different Environments.Molecules (Basel, Switzerland) · 2022Article
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- Stepping forward in antibody-drug conjugate development.Pharmacology & therapeutics · 2022Review
- Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist's Perspective.Antibodies (Basel, Switzerland) · 2021Review
- Antibody-Drug Conjugates: The Last Decade.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Antibody-Drug Conjugates: The New Frontier of Chemotherapy.International journal of molecular sciences · 2020Review
- Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Article
- Antibody-Drug Conjugates for the Treatment of Hematological Malignancies: A Comprehensive Review.Targeted oncology · 2018Review
- Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?Antibodies (Basel, Switzerland) · 2018Review
- Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?British journal of cancer · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The development of antibody-drug conjugates (ADC), a promising class of anticancer agents, has traditionally relied on the use of antibodies capable of selective internalization in tumor cells. We have recently shown that also noninternalizing antibodies, coupled to cytotoxic drugs by means of disulfide linkers that can be cleaved in the tumor extracellular environment, can display a potent therapeutic activity. Here, we have compared the tumor-targeting properties, drug release rates, and therapeutic performance of two ADCs, based on the maytansinoid DM1 thiol drug and on the F8 antibody, directed against the alternatively spliced Extra Domain A (EDA) domain of fibronectin. The antibody was used in IgG or in small immune protein (SIP) format. In both cases, DM1 was coupled to unpaired cysteine residues, resulting in a drug-antibody ratio of 2. In biodistribution studies, SIP(F8)-SS-DM1 accumulated in the tumor and cleared from circulation more rapidly than IgG(F8)-SS-DM1. However, the ADC based on the IgG format exhibited a higher tumor uptake at later time points (e.g., 33%IA/g against 8%IA/g at 24 hours after intravenous administration). In mouse plasma, surprisingly, the ADC products in IgG format were substantially more stable compared with the SIP format (half-lives >48 hours and <3 hours at 37°C, respectively), revealing a novel mechanism for the control of disulfide-based drug release rates. Therapy experiments in immunocompetent mice bearing murine F9 tumors revealed that SIP(F8)-SS-DM1 was more efficacious than IgG(F8)-SS-DM1 when the two products were compared either in an equimolar basis or at equal milligram doses.
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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.