Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side effect of anticancer treatments, often leading to chronic pain and loss of sensation. Antibody-drug conjugates (ADCs), while effective in targeting tumors, have demonstrated unexpected neurotoxicity. To improve preclinical screening, 28bio developed NerveSim®, a Complex In Vitro Model (CIVM) incorporating human iPSC-derived sensory neurons and human primary Schwann cells.
NerveSim® was tested in both 2D coculture and 3D Nerve-on-a-Chip models. The 3D model allowed for a more complex neural environment, providing electrophysiological endpoints. Both models were evaluated for CIPN detection using metrics such as neurite length, Schwann cell circularity, electrophysiology, and nerve fiber length.
Seven chemotherapeutics, including ADCs and small molecule drugs, were tested. The 3D Nerve-on-a-Chip model's electrophysiology endpoint proved to be the most sensitive, detecting CIPN effects at significantly lower concentrations than the 2D model. ADCs and oxaliplatin showed the most pronounced discrepancy, with the 3D model outperforming traditional 2D metrics.
The NerveSim® 3D Nerve-on-a-Chip model offers superior sensitivity in detecting chemotherapy-induced peripheral neuropathy, particularly for ADCs. This advancement could significantly improve preclinical screening and reduce unexpected clinical neurotoxicity outcomes.
