Improving Therapeutic Efficacy For Brain-Based Cancers Using NEO 100

NEO 100 Enables Brain Delivery Of Blood-Brain Barrier-Impermeable Therapeutics.

Authors: Weijun Wang ¹, Nagore I. Marín-Ramos¹, Haiping He^1,2, Shan Zeng^1,2, Hee-Yeon Cho¹, Stephen D. Swenson¹, Long Zheng³, Alan L. Epstein³, Axel H. Schönthal⁴, Florence M. Hofman³, Ligang Chen², and Thomas C. Chen^1,4

NeOnc Technologies conducted a study of its NEO 100 Perillyl Alcohol (POH) formulation to determine its in vitro Blood-Brain Barrier (BBB) permeability using transepithelial/transendothelial electrical resistance (TEER) and antibody diffusion
assays. Ultrasound-guided intracardiac administration of NEO100, followed by intravenous application of Evan’s blue, methotrexate, checkpoint-inhibitory antibodies, or CAR T-cells was conducted on mouse models.

The study showed that NEO 100 opened the BBB in a reversible and non-toxic fashion in vitro and in vivo. It enabled greatly increased brain entry of all tested therapeutics and was well tolerated by animals. Mechanistic studies revealed the effects of NEO 100 on different BBB transport pathways, along with translocation of tight junction proteins from the membrane to the cytoplasm in brain endothelial cells.

¹ Department of Neurological Surgery, USC, ²Department of Neurosurgery, Affiliated
Hospital of Southwest Medical University, Luzhou 646000, China, ³Department of Pathology, Keck School of Medicine, The University of Southern California (USC), Los Angeles, CA 90033, USA, ⁴Department of Microbiology and Immunology, Keck School of Medicine, The University of Southern California (USC), Los Angeles, CA 90033, USA