This study focuses on evaluating potential off-target peripheral neuropathy (PN) risks posed by Antibody-Drug Conjugates (ADCs) and other chemotherapeutics. ADCs deliver potent cancer therapies but may induce PN through various mechanisms, including bystander effects.
A co-culture system combining human iPSC-derived sensory neurons (hSNs) and primary human Schwann cells (hSCs) was developed. Cells were plated in a 96-well format for high-throughput screening and exposed to various test articles, including Paclitaxel, Oxaliplatin, Bortezomib, Vincristine, and MMAE. The system was optimized for cell health, distribution, attachment, and outgrowth.
The co-culture system effectively characterized cell-specific responses to these known PN-causing agents. Key metrics such as cell count, neurite length, processes, branches, and Schwann cell circularity were measured, revealing insights into toxicity mechanisms. The system demonstrated value in identifying ADC candidates with lower PN risks.
This dual human cell system offers a fast, cost-effective method for assessing off-target PN risks in ADC and chemotherapeutic development. Its potential for high-content screening makes it a valuable tool in identifying safer therapeutic candidates.
