EXTH-84. A DURABLE RECURRENT INTRACEREBROVENTRICULAR INFUSION METHOD IN MICE FOR PRECLINICAL ASSESSMENT OF CELLULAR THERAPEUTICS

Abstract BACKGROUND Significant advancement in cellular treatments for glioblastoma has been made in recent years. The administration route has shifted from intravenous access to local delivery, namely intracerebroventricular (ICV) delivery, in order to prevent the injected cellular products from becoming trapped in peripheral organs such as liver and spleen. There is currently no reliable preclinical system available to accurately examine new cellular treatments that involve long-term recurrent infusion into the cerebral ventricles. METHOD We optimized the surgical device and technique by modifying a commercially available ICV device with a predetermined needle length, eliminating the requirement for spacers hence relieving the tension of the surgical wounds. To avoid skin puncture, we substituted the tunneled catheter with a silicon catheter. The surgical incisions were secured with autoclips in replacement of sutures. We administered periodic infusions of engineered monocytes on a weekly basis using the tunneled catheter for a duration of 8 weeks. The rate of wound dehiscence was monitored. RESULTS The delivery of the engineered monocytes to the cerebral ventricle via the ICV device has been confirmed using a bioluminescence-based imaging. The device and the tunneled catheter demonstrate a long-lasting durability for a minimum of 8 weeks. The optimized device and method effectively reduce the occurrence of post-operative wound dehiscence. Using a silicon catheter minimizes skin punctures. CONCLUSION Our optimized ICV device, material, and surgical approach offer a dependable preclinical instrument for the long-term and recurrent delivery of cellular therapies that reflect patients’ clinical treatment schedules and provide a more accurate evaluation of their translational potential.