biOasis Technologies Ord Shs BIOAF

CAR-T and Convection Enhanced Delivery

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Convection Enhanced Delivery of Human Car T Cells Using a Low Viscosity Hydrogel

Final Number:
1265

Authors:
Ahmet F Atik MD; Carter M. Suryadevara BS; Luis Sanchez-Perez PhD; Gary E. Archer; Peter Edward Fecci; John H. Sampson MD, PhD, MHSc, MBA

Study Design:
Laboratory Investigation

Subject Category:

Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

Introduction: Convection Enhanced Delivery (CED) improves the distribution of therapeutics in the intracranial space and overcomes treatment limitations due to the Blood Brain Barrier. Although CED successfully delivers small therapeutic agents, sedimentation inside the pump and extension tube limits the delivery of therapeutic cells; the traditional CED saline carrier can only deliver 4.6 % of CAR T cells to the target location. We developed a biomaterial that acts as a scaffold for CAR T cells and maintains a homogenous cell distribution throughout the matrix due to it's higher viscosity and webby structure.

Methods: Carrier delivery: We established the CED setup currently used in clinical trials at Duke University Hospital (BD Infusion pump medfusion 3010a, 20 ml syringes and Phoenix neuro PIT400 infusion pump). CAR T cells are resuspended in either hydrogel or saline, loaded into a 20 ml syringe and connected to an Eppendorf tube. Outcome infusate is counted hourly for 5 hours, using the Trypan Blue Cell Counting Method. CED and Cytotoxicity Assay: U87 and U87vIII tumor lines were used as targets in CTL assays with EGFRvIII CAR T cells suspended in either hydrogel or saline as a CED treatment. After 5 hours of infusion, both infusates were compared to fresh hydrogel and saline groups in cytotoxicity assays.

Results: Post CED average yields are, 57% of CAR T cells in the hydrogel carrier survived versus 4.6% in the saline carrier. Furthermore, these cells have a cytotoxicity similar to fresh hydrogel and saline carrier groups.

Conclusions: Hydrogel is a biodegradable biomaterial that provides the successful delivery of therapeutic cells via CED and maintains a homogenous distribution of these cells with control levels of cytotoxicity. Low viscosity hyaluronic acid hydrogel is an alternative carrier to saline in the CED of CAR T cells.

Patient Care: This method overcomes a significant problem in CED of cells and provide effective treatment against glioblastome.

Learning Objectives: Biodegradable hyaluronic acid based hydrogel can provide superior cell transfer yield to traditional carriers. CARs in final infusate is as effective as uninfused CAR T cells against GBM.