title: Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy.
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.
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Tsao
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.forename: Ali
authors.initials: A
authors.lastname: Ravanpay
authors.forename: Ariane E
authors.initials: AE
authors.lastname: Erickson
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D003470:Culture Media; D003602:Cytotoxicity, Immunologic; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D016219:Immunotherapy, Adoptive; D011092:Polyethylene Glycols / Q000737:chemistry*; D013601:T-Lymphocytes / Q000502:physiology*; D054457:Tissue Scaffolds; D044366:Transition Temperature
chemical_list: D003470:Culture Media; D020100:Hydrogels; D011092:Polyethylene Glycols; D048271:Chitosan