ArticleFrontiers in toxicology2026
Integrated electrophysiological and payload-release assessment of neuronal responses to antibody-drug conjugates in human iPSC-derived sensory neurons: implications for
Article in Frontiers in toxicology, 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
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) enable tumor-specific drug delivery; however, target antigen-independent adverse events, including peripheral neuropathy, remain a significant clinical concern. The mechanisms underlying ADC-induced neurotoxicity, particularly the relationship between payload release and alterations in neuronal function, are not yet fully understood. In this study, we established an analytical platform that integrates microelectrode array (MEA) recordings using human induced pluripotent stem cell (iPSC)-derived sensory neurons with quantitative measurement of payload levels detected after ADC exposure under culture conditions, enabling functional evaluation of the direct effects of ADCs and their payloads on neuronal activity. The microtubule inhibitors monomethyl auristatin E (MMAE) and Lys-SMCC-DM1, when administered as free payloads, suppressed neuronal activity, as indicated by reduced firing rates, decreased spike amplitudes, together with neurite fragmentation. In contrast, their corresponding ADCs, brentuximab vedotin and trastuzumab emtansine, showed limited detectable effects on neuronal activity under the present experimental conditions. Conversely, the topoisomerase I inhibitor SN-38 enhanced neuronal activity, as evidenced by increased firing rates and spike amplitudes without marked morphological disruption. Similar functional changes were observed with sacituzumab govitecan. Furthermore, quantitative analysis revealed substantially higher measured payload levels at the 168-h endpoint following sacituzumab govitecan exposure than following brentuximab vedotin or trastuzumab emtansine exposure under the present experimental conditions. These findings suggest that the neuronal functional responses observed following ADC exposure may be associated with differences in measured payload levels and are consistent with the possibility of target antigen-independent effects. The integrated platform developed in this study enables quantitative assessment of neuronal functional responses to ADCs and payloads and may serve as a complementary tool for
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.