ArticleOncotarget2019
Biodistribution and efficacy of an anti-TENB2 antibody-drug conjugate in a patient-derived model of prostate cancer.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Trial watch: antibody-drug conjugates in cancer therapy.Oncoimmunology · 2026Review
- Through every lens: assessing the impact of chemical modifications on antibody-conjugates using in vivo imaging.Npj imaging · 2025Review
- Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data.Science advances · 2024Review
- Reducing target binding affinity improves the therapeutic index of anti-MET antibody-drug conjugate in tumor bearing animals.PloS one · 2024Article
- Intravital Microscopy Reveals Unforeseen Biodistribution Within the Liver and Kidney Mechanistically Connected to the Clearance of a Bifunctional Antibody.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- New Technologies Bloom Together for Bettering Cancer Drug Conjugates.Pharmacological reviews · 2022Review
- Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.Journal of medicinal chemistry · 2022Article
- Predictive Simulations in Preclinical Oncology to Guide the Translation of Biologics.Frontiers in pharmacology · 2022Article
- Antibody Co-Administration Can Improve Systemic and Local Distribution of Antibody-Drug Conjugates to IncreaseMolecular cancer therapeutics · 2021Article
- Analytical Methods for the Detection and Quantification of ADCs in Biological Matrices.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Co-administered antibody improves penetration of antibody-dye conjugate into human cancers with implications for antibody-drug conjugates.Nature communications · 2020Article
- Impact of Physiologically Based Pharmacokinetics, Population Pharmacokinetics and Pharmacokinetics/Pharmacodynamics in the Development of Antibody-Drug Conjugates.Journal of clinical pharmacology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TENB2, a transmembrane proteoglycan protein, is a promising target for antibody drug conjugate (ADC) therapy due to overexpression in human prostate tumors and rapid internalization. We previously characterized how predosing with parental anti-TENB2 monoclonal antibody (mAb) at 1 mg/kg in a patient-derived LuCap77 explant model with high (3+) TENB2 expression could (i) block target-mediated intestinal uptake of tracer (& 0.1 mg/kg) levels of radiolabeled anti-TENB2-monomethyl auristatin E ADC while preserving tumor uptake, and (ii) maintain efficacy relative to ADC alone. Here, we systematically revisit this strategy to evaluate the effects of predosing on tumor uptake and efficacy in LuCap96.1, a low TENB2-expressing (1+) patient-derived model that is more responsive to ADC therapy than LuCap77. Importantly, rather than using tracer (& 0.1 mg/kg) levels, radiolabeled ADC tumor uptake was assessed at 1 mg/kg - one of the doses evaluated in the tumor growth inhibition study - in an effort to bridge tissue distribution (PK) with efficacy (PD). Predosing with mAb up to 1 mg/kg had no effect on efficacy. These findings warrant further investigations to determine whether predosing prior to ADC therapy might improve therapeutic index by preventing ADC disposition and possible toxicological liabilities in antigen-expressing healthy tissues.
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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.