ArticlePharmaceutics2021
Pharmacokinetics and Pharmacodynamics of T-Cell Bispecifics in the Tumour Interstitial Fluid.
Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 8 citations in OpenAlex.
- Cancer-associated alterations in O-GalNAc glycosylation.Glycobiology · 2026Review
- Quantitative Investigation of ATP Switch Concept of STA551 Through Combined In Vivo Tissue Distribution Studies and Physiologically Based Pharmacokinetic Modeling.The AAPS journal · 2026Article
- [EJNMMI physics · 2026Article
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Increased longevity of circulating human IgG in an NSG Fc gamma receptor-1 deficient humanized mouse model.Journal of pharmaceutical sciences · 2025Article
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- Interspecies Brain PBPK Modeling Platform to Predict Passive Transport through the Blood-Brain Barrier and Assess Target Site Disposition.Pharmaceutics · 2024Article
- Combining mathematical modeling,Frontiers in pharmacology · 2024Article
- A model-based approach leveraging in vitro data to support dose selection from the outset: A framework for bispecific antibodies in immuno-oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
- Preclinical InVivo Data Integrated in a Modeling Network Informs a Refined Clinical Strategy for a CD3 T-Cell Bispecific in Combination with Anti-PD-L1.The AAPS journal · 2022Article
- Investigating brain uptake of a non-targeting monoclonal antibody after intravenous and intracerebroventricular administration.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The goal of this study is to investigate the pharmacokinetics in plasma and tumour interstitial fluid of two T-cell bispecifics (TCBs) with different binding affinities to the tumour target and to assess the subsequent cytokine release in a tumour-bearing humanised mouse model. Pharmacokinetics (PK) as well as cytokine data were collected in humanised mice after iv injection of cibisatamab and CEACAM5-TCB which are binding with different binding affinities to the tumour antigen carcinoembryonic antigen (CEA). The PK data were modelled and coupled to a previously published physiologically based PK model. Corresponding cytokine release profiles were compared to in vitro data. The PK model provided a good fit to the data and precise estimation of key PK parameters. High tumour interstitial concentrations were observed for both TCBs, influenced by their respective target binding affinities. In conclusion, we developed a tailored experimental method to measure PK and cytokine release in plasma and at the site of drug action, namely in the tumour. Integrating those data into a mathematical model enabled to investigate the impact of target affinity on tumour accumulation and can have implications for the PKPD assessment of the therapeutic antibodies.
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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.