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Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells.

Publication ,  Journal Article
Atik, AF; Suryadevara, CM; Schweller, RM; West, JL; Healy, P; Herndon Ii, JE; Congdon, KL; Sanchez-Perez, L; McLendon, RE; Archer, GE; Fecci, P ...
Published in: J Clin Neurosci
October 2018

Convection Enhanced Delivery (CED) infuses therapeutic agents directly into the intracranial area continuously under pressure. The convection improves the distribution of therapeutics such as those aimed at brain tumors. Although CED successfully delivers small therapeutic agents, this technique fails to effectively deliver cells largely due to cell sedimentation during delivery. To overcome this limitation, we have developed a low viscosity hydrogel (LVHydrogel), which is capable of retaining cells in suspension. In this study, we evaluated whether LVHydrogel can effectively act as a carrier for the CED of tumor-specific chimeric antigen receptor (CAR) T cells. CAR T cells were resuspended in saline or LVHydrogel carriers, loaded into syringes, and passed through the CED system for 5 h. CAR T cells submitted to CED were counted and the efficiency of delivery was determined. In addition to delivery, the ability of CAR T cells to migrate and induce cytotoxicity was evaluated. Our studies demonstrate that LVHydrogel is a superior carrier for CED in comparison to saline. The efficiency of cell delivery in saline carrier was only ∼3-5% of the total cells whereas delivery by the LVHydrogel carrier was much higher, reaching ∼45-75%. Migration and Cytotoxicity was similar in both carriers in non-infused samples but we found superior cytotoxicity in LVHydrogel group post-infusion. We demonstrate that LVHydrogel, a biodegradable biomaterial which does not cause acute toxicity on preclinical animal models, prevents cellular sedimentation during CED and presents itself as a superior carrier to the current carrier, saline, for the CED of CAR T cells.

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Published In

J Clin Neurosci

DOI

EISSN

1532-2653

Publication Date

October 2018

Volume

56

Start / End Page

163 / 168

Location

Scotland

Related Subject Headings

  • Viscosity
  • T-Lymphocytes
  • Receptors, Chimeric Antigen
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Immunotherapy, Adoptive
  • Hydrogels
  • Hyaluronic Acid
 

Citation

APA
Chicago
ICMJE
MLA
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Atik, A. F., Suryadevara, C. M., Schweller, R. M., West, J. L., Healy, P., Herndon Ii, J. E., … Sampson, J. H. (2018). Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells. J Clin Neurosci, 56, 163–168. https://doi.org/10.1016/j.jocn.2018.06.005
Atik, Ahmet F., Carter M. Suryadevara, Ryan M. Schweller, Jennifer L. West, Patrick Healy, James E. Herndon Ii, Kendra L. Congdon, et al. “Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells.J Clin Neurosci 56 (October 2018): 163–68. https://doi.org/10.1016/j.jocn.2018.06.005.
Atik AF, Suryadevara CM, Schweller RM, West JL, Healy P, Herndon Ii JE, et al. Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells. J Clin Neurosci. 2018 Oct;56:163–8.
Atik, Ahmet F., et al. “Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells.J Clin Neurosci, vol. 56, Oct. 2018, pp. 163–68. Pubmed, doi:10.1016/j.jocn.2018.06.005.
Atik AF, Suryadevara CM, Schweller RM, West JL, Healy P, Herndon Ii JE, Congdon KL, Sanchez-Perez L, McLendon RE, Archer GE, Fecci P, Sampson JH. Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells. J Clin Neurosci. 2018 Oct;56:163–168.
Journal cover image

Published In

J Clin Neurosci

DOI

EISSN

1532-2653

Publication Date

October 2018

Volume

56

Start / End Page

163 / 168

Location

Scotland

Related Subject Headings

  • Viscosity
  • T-Lymphocytes
  • Receptors, Chimeric Antigen
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Immunotherapy, Adoptive
  • Hydrogels
  • Hyaluronic Acid