In an article published in the Journal of Neurosurgery website, the study results were posted on Neonc Technologies Holdings’ recent animal study looking at the efficacy of using the NEO100 formulation for treating CNS disease in the brain. Malignancies of the CNS are difficult to treat because the blood-brain barrier (BBB) prevents most therapeutics from reaching the intracranial lesions at sufficiently high concentrations. This also applies to chimeric antigen receptor (CAR) T cells, for which systemic delivery is inferior to direct intratumoral or intraventricular injection of the
cells.

In the study, human Raji lymphoma cells were implanted into the brains of immune-deficient mice. After tumor uptake was confirmed with bioluminescent imaging, 0.3% NEO100 was injected intra-arterially, followed by intravenous (IV) delivery of CD19-targeted CAR T cells. After this single intervention, tumor growth was monitored with imaging, the long-term survival of mice was recorded, and select mice were euthanized to analyze the distribution of CAR T cells in brain tissue.

Intravenously injected CAR T cells could be readily detected in brain tumor areas after IA injection of NEO100 but not after IA injection of the vehicle (without NEO100). Although all untreated control animals died within 3 weeks, all mice that received IA NEO100 followed by IV CAR T cells survived and thrived for 200 days, when the experiment was terminated. Of the mice that received IV CAR T cells without prior IA NEO100, 3 died within 3 weeks and 2 survived long-term.

In conclusion, the BBB opening by IA NEO100 facilitates brain entry of intravenously delivered CD19 CAR T cells. The long-term survival of all mice with CNS lymphoma, along with the disappearance of the tumor as determined with imaging, suggests that this one-time therapeutic intervention was curative. BBB opening by IA NEO100 may offer a novel option to increase brain access by CAR T cells.

Read The Paper

Enhancing brain entry and therapeutic activity of chimeric antigen receptor T cells with intra-arterial NEO100 in a mouse model of CNS lymphoma.

Authors: *Wenjun Wang¹, Haiping He, MD², Long Zheng, PhD³, Shan Zeng, MD², Hee-Yeon Cho, PhD¹, Aida Kouhi, PhD³, Leslie A. Khawli, PhD³, Ligang Chen, MD, PhD², Apostolos Stathopoulos, MD, PhD^1,4, Axel H. Schönthal, PhD⁵, Alan L. Epstein, MD, PhD^3,6, and Thomas C. Chen^1,3,6,

Departments of ¹Neurological Surgery, ³Pathology, and ⁵Molecular Microbiology and Immunology, Keck School of Medicine,
University of Southern California, Los Angeles, California; ²Department of Neurosurgery, Affiliated Hospital of Southwest
Medical University, Luzhou, China; ⁴Department of Neurosurgery, Henry Dunant Hospital Center, Athens, Greece; and ⁶Norris
Comprehensive Cancer Center, University of Southern California, Los Angeles, California