ArticleFluids and barriers of the CNS2026
Translational applicability of human blood-brain barrier spheroid models for the development of brain-penetrant therapeutic antibodies.
Article in Fluids and barriers of the CNS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Drug delivery systems play a key role in the development of new therapeutic strategies for brain diseases. Antibodies capable of crossing the blood–brain barrier (BBB) have attracted considerable attention as promising drug carriers. To facilitate their development, we previously established human multi-cellular spheroidal (hMCS)-BBB models as microphysiological system-based platforms. In this study, we aimed to enhance the applicability of these hMCS-BBB models for the development of brain-permeable antibodies using four anti-human transferrin receptor monoclonal antibodies (hTfRMAbs). Permeability assays using hMCS-BBB models revealed BBB permeability in three out of four hTfRMAbs, with two antibodies exhibiting Km values of 6.5 and 12.0 µg/mL, respectively. Importantly, differences in the BBB permeability of tested hTfRMAbs were consistent with the brain permeability profiles reported in monkeys in vivo. Moreover, these differences were not detected via simple uptake assays using monoculture brain microvascular endothelial cells, highlighting the superior evaluation potential of hMCS-BBB models. Lysosome co-localization assays using hMCS-BBB models revealed the distinct intracellular localization patterns of BBB-permeable and non-permeable hTfRMAbs with lysosomes, presumably explaining their different permeability properties. Overall, hMCS-BBB models effectively characterized the BBB permeability of hTfRMAbs, demonstrated strong potential for in vivo extrapolation, and proved suitable for mechanistic studies of the cellular pathways regulating their BBB permeability. Therefore, hMCS-BBB models are considered promising tools for advancing the development of brain-permeable therapeutic antibodies.
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.