2026-10-12T07:31:59Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33980578 2026-09-24T07:24:05Z category_44 portal_316 item_type_3 month_year_09_2026

Table 1_Integrated electrophysiological and payload-release assessment of neuronal responses to antibody-drug conjugates in human iPSC-derived sensory neurons: implications for in vitro neurotoxicity evaluation.xlsx Taeko Kuroda (14369547) Xiaobo Han (2869802) Toshiki Mochizuki (5228336) Yuto Ishibashi (14369550) Aya Goto (4988696) Yuki Seki (4988693) Norimasa Miyamoto (9491) Takashi Yoshinaga (461969) Shoji Asakura (15342411) Ikuro Suzuki (4629046) Toxicology antibody-drug conjugates human iPSC-derived sensory neurons microelectrode array neurotoxicity payload release peripheral neuropathy <p>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 in vitro neurotoxicity evaluation during ADC design and development.</p> 2026-09-24T07:24:05Z Dataset Dataset 10.3389/ftox.2026.1855330.s005 https://figshare.com/articles/dataset/Table_1_Integrated_electrophysiological_and_payload-release_assessment_of_neuronal_responses_to_antibody-drug_conjugates_in_human_iPSC-derived_sensory_neurons_implications_for_in_vitro_neurotoxicity_evaluation_xlsx/33980578 CC BY 4.0