ArticleMolecular cancer therapeutics2021
Antibody Co-Administration Can Improve Systemic and Local Distribution of Antibody-Drug Conjugates to Increase
Article in Molecular cancer therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- Combining antibody conjugates with cytotoxic and immune-stimulating payloads maximizes anti-cancer activity.Molecular oncology · 2026Article
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Antibody-drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives.NPJ breast cancer · 2025Review
- Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index.Cancers · 2025Review
- Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Optimizing Solid Tumor Treatment with Antibody-drug Conjugates Using Agent-Based Modeling: Considering the Role of a Carrier Dose and Payload Class.Pharmaceutical research · 2024Article
- Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data.Science advances · 2024Review
- Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates.Molecular cancer therapeutics · 2024Article
- [Science advances · 2024Article
- Validity conditions of approximations for a target-mediated drug disposition model: A novel first-order approximation and its comparison to other approximations.PLoS computational biology · 2024Article
- Improving Intracellular Delivery of an Antibody-Drug Conjugate Targeting Carcinoembryonic Antigen Increases Efficacy at Clinically Relevant Doses In Vivo.Molecular cancer therapeutics · 2024Article
- Impact of tissue penetration and albumin binding on design of T cell targeted bispecific agents.Neoplasia (New York, N.Y.) · 2024Article
- Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.The Journal of pharmacology and experimental therapeutics · 2023Article
- A cross-reactive pH-dependent EGFR antibody with improved tumor selectivity and penetration obtained by structure-guided engineering.Molecular therapy oncolytics · 2022Article
- BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for Treatment of Solid Tumors.Molecular cancer therapeutics · 2022Article
- Pharmacokinetics and Pharmacodynamics of TAK-164 Antibody Drug Conjugate Coadministered with Unconjugated Antibody.The AAPS journal · 2022Article
- Design of high avidity and low affinity antibodies for in situ control of antibody drug conjugate targeting.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Several antibody-drug conjugates (ADC) showing strong clinical responses in solid tumors target high expression antigens (HER2, TROP2, Nectin-4, and folate receptor alpha/FRα). Highly expressed tumor antigens often have significant low-level expression in normal tissues, resulting in the potential for target-mediated drug disposition (TMDD) and increased clearance. However, ADCs often do not cross-react with normal tissue in animal models used to test efficacy (typically mice), and the impact of ADC binding to normal tissue antigens on tumor response remains unclear. An antibody that cross-reacts with human and murine FRα was generated and tested in an animal model where the antibody/ADC bind both human tumor FRα and mouse FRα in normal tissue. Previous work has demonstrated that a "carrier" dose of unconjugated antibody can improve the tumor penetration of ADCs with high expression target-antigens. A carrier dose was employed to study the impact on cross-reactive ADC clearance, distribution, and efficacy. Co-administration of unconjugated anti-FRα antibody with the ADC-improved efficacy, even in low expression models where co-administration normally lowers efficacy. By reducing target-antigen-mediated clearance in normal tissue, the co-administered antibody increased systemic exposure, improved tumor tissue penetration, reduced target-antigen-mediated uptake in normal tissue, and increased ADC efficacy. However, payload potency and tumor antigen saturation are also critical to efficacy, as shown with reduced efficacy using too high of a carrier dose. The judicious use of higher antibody doses, either through lower DAR or carrier doses, can improve the therapeutic window by increasing efficacy while lowering target-mediated toxicity in normal tissue.
Indexed as
Identifiers
What OpenQuestion holds
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.