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

Tsao CT, Kievit FM, Ravanpay A, Erickson AE, Jensen MC, Ellenbogen RG, Zhang M - Biomacromolecules (2014)

Bottom Line: Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors.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.Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

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.

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Rheological properties of PCgel. (a) Shearviscosity and (b) storagemodulus (G′) and loss modulus (G″) as a function of temperature.
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fig2: Rheological properties of PCgel. (a) Shearviscosity and (b) storagemodulus (G′) and loss modulus (G″) as a function of temperature.

Mentions: The sol-to-gel transition behavior of PCgel was tested byrheologicalanalyses. Figure 2a shows the viscosity ofthe PCgel as a function of temperature. The viscosity slightly decreasedas the temperature increased from 4 to ∼25 °C. When thetemperature approached 25–30 °C, an abrupt and significantincrease in viscosity was observed. The viscosity remained at theelevated constant level after the temperature reached 32 °C untilthe temperature reached 45 °C. Figure 2b represents the changes in the storage modulus (G′) and the loss modulus (G″) for thePCgel as a function of temperature.


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

Tsao CT, Kievit FM, Ravanpay A, Erickson AE, Jensen MC, Ellenbogen RG, Zhang M - Biomacromolecules (2014)

Rheological properties of PCgel. (a) Shearviscosity and (b) storagemodulus (G′) and loss modulus (G″) as a function of temperature.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215871&req=5

fig2: Rheological properties of PCgel. (a) Shearviscosity and (b) storagemodulus (G′) and loss modulus (G″) as a function of temperature.
Mentions: The sol-to-gel transition behavior of PCgel was tested byrheologicalanalyses. Figure 2a shows the viscosity ofthe PCgel as a function of temperature. The viscosity slightly decreasedas the temperature increased from 4 to ∼25 °C. When thetemperature approached 25–30 °C, an abrupt and significantincrease in viscosity was observed. The viscosity remained at theelevated constant level after the temperature reached 32 °C untilthe temperature reached 45 °C. Figure 2b represents the changes in the storage modulus (G′) and the loss modulus (G″) for thePCgel as a function of temperature.

Bottom Line: Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors.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.Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

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.

Show MeSH
Related in: MedlinePlus