Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy

Ching Ting Tsao, Forrest M. Kievit, Ali Ravanpay, Ariane E. Erickson, Michael C. Jensen, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The outcome for glioblastoma patients remains dismal for its invariably recrudesces within 2 cm of the resection cavity. Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors. Here, we report the development of a biodegradable hydrogel containing therapeutic T lymphocytes for localized delivery to glioblastoma cells for brain tumor immunotherapy. Thermoreversible poly(ethylene glycol)-g-chitosan hydrogels (PCgels) were optimized for steady T lymphocyte release. Nuclear magnetic resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)-g-chitosan, and rheological studies revealed that the sol-to-gel transition of the PCgel occurred around ≥32 °C. T lymphocyte invasion through the PCgel and subsequent cytotoxicity to glioblastoma were assessed in vitro. The PCgel was shown to be cellular compatible with T lymphocytes, and the T lymphocytes retain their anti-glioblastoma activity after being encapsulated in the PCgel. T lymphocytes in the PCgel were shown to be more effective in killing glioblastoma than those in the Matrigel control. This may be attributed to the optimal pore size of the PCgel allowing better invasion of T lymphocytes. Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

Original languageEnglish (US)
Pages (from-to)2656-2662
Number of pages7
JournalBiomacromolecules
Volume15
Issue number7
DOIs
StatePublished - Jul 14 2014

Fingerprint

T-cells
Hydrogel
Glioblastoma
Chitosan
Hydrogels
Immunotherapy
Polyethylene glycols
T-Lymphocytes
Therapeutics
Tumors
Polymethyl Methacrylate
Cytotoxicity
Sols
PEG-graft-trimethyl-chitosan copolymer
Brain Neoplasms
Nuclear magnetic resonance spectroscopy
Pore size
Brain
Magnetic Resonance Spectroscopy
Gels

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy. / Tsao, Ching Ting; Kievit, Forrest M.; Ravanpay, Ali; Erickson, Ariane E.; Jensen, Michael C.; Ellenbogen, Richard G.; Zhang, Miqin.

In: Biomacromolecules, Vol. 15, No. 7, 14.07.2014, p. 2656-2662.

Research output: Contribution to journalArticle

Tsao, Ching Ting ; Kievit, Forrest M. ; Ravanpay, Ali ; Erickson, Ariane E. ; Jensen, Michael C. ; Ellenbogen, Richard G. ; Zhang, Miqin. / Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy. In: Biomacromolecules. 2014 ; Vol. 15, No. 7. pp. 2656-2662.
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