ArticleScientific reports2022
Design of high avidity and low affinity antibodies for in situ control of antibody drug conjugate targeting.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Exploring the immunological effects of antibody-drug conjugates.Nature reviews. Clinical oncology · 2026Review
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- Microsystem technologies for accelerating the discovery and translation of immunotherapies.Nature reviews. Drug discovery · 2026Review
- Novel fully human IgG1 targeting folate receptor α demonstrates antitumor efficacy driven by avidity rather than monovalent binding affinity.Scientific reports · 2025Article
- Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity.The AAPS journal · 2025Article
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- A New Approach to Examine Cell-Antibody Avidity with Surface Plasmon Resonance Imaging.Biosensors · 2025Article
- Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index.Cancers · 2025Review
- Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.The Journal of pharmacology and experimental therapeutics · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Antibody-Drug Conjugates (ADCs) have rapidly expanded in the clinic, with 7 new approvals in 3 years. For solid tumors, high doses of ADCs improve tissue penetration and efficacy. These doses are enabled by lower drug-to-antibody ratios and/or co-administration of unconjugated antibody carrier doses to avoid payload toxicity. While effective for highly expressed targets, these strategies may not maintain efficacy with lower target expression. To address this issue, a carrier dose that adjusts binding in situ according to cellular expression was designed using computational modeling. Previous studies demonstrated that coadministration of unconjugated antibody with the corresponding ADC at an 8:1 ratio improves ADCs efficacy in high HER2 expressing tumors. By designing a High Avidity, Low Affinity (HALA) carrier antibody, ADC binding is partially blocked in high expression cells, improving tissue penetration. In contrast, the HALA antibody cannot compete with the ADC in low expressing cells, allowing ADC binding to the majority of receptors. Thus, the amount of competition from the carrier dose automatically adjusts to expression levels, allowing tailored competition between different patients/metastases. The computational model highlights two dimensionless numbers, the Thiele modulus and a newly defined competition number, to design an optimal HALA antibody carrier dose for any target.
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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.