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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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Time courseof therapeutic T lymphocyte invasion through the PCgeland Matrigel. The statistical differences in therapeutic T lymphocyteinvasion through the PCgel vs through Matrigel are labeled with asterisks(p < 0.05).
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fig5: Time courseof therapeutic T lymphocyte invasion through the PCgeland Matrigel. The statistical differences in therapeutic T lymphocyteinvasion through the PCgel vs through Matrigel are labeled with asterisks(p < 0.05).

Mentions: The increased capacity of the PCgel for T lymphocytes toinvadewas further confirmed through quantification of cells in a transwellinvasion assay (Figure 5). It was found that4 times as many T lymphocytes invaded through the PCgel as comparedto Matrigel after 100 h. In addition, sustained invasion of T lymphocytesthrough the PCgel was observed with an approximately linear increasein the number of invaded T lymphocytes over time. This was likelya result of the appropriate pore size and biocompatibility of thePCgel for T lymphocytes.


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)

Time courseof therapeutic T lymphocyte invasion through the PCgeland Matrigel. The statistical differences in therapeutic T lymphocyteinvasion through the PCgel vs through Matrigel are labeled with asterisks(p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Time courseof therapeutic T lymphocyte invasion through the PCgeland Matrigel. The statistical differences in therapeutic T lymphocyteinvasion through the PCgel vs through Matrigel are labeled with asterisks(p < 0.05).
Mentions: The increased capacity of the PCgel for T lymphocytes toinvadewas further confirmed through quantification of cells in a transwellinvasion assay (Figure 5). It was found that4 times as many T lymphocytes invaded through the PCgel as comparedto Matrigel after 100 h. In addition, sustained invasion of T lymphocytesthrough the PCgel was observed with an approximately linear increasein the number of invaded T lymphocytes over time. This was likelya result of the appropriate pore size and biocompatibility of thePCgel for T lymphocytes.

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