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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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Percentage of U-87 MG tumor cell death afterT lymphocyte treatmentat various effector/target (T lymphocyte/U87) ratios (1/0, 3/1 to100/1). Mock was applied as a negative control.
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fig6: Percentage of U-87 MG tumor cell death afterT lymphocyte treatmentat various effector/target (T lymphocyte/U87) ratios (1/0, 3/1 to100/1). Mock was applied as a negative control.

Mentions: To decide the ratio of T cells to U-87 MG cellsfor optimized tumor cell death, different amounts of T lymphocyteswere added 2 h after 1 × 104 U-87 MG cells had beenseeded. AlamarBlue was used to quantify the number of viable U-87MG cells, which was quantified by AlamarBlue after T lymphocytes wereadded for 24 h and each well was washed thrice with PBS to ensureno residual T lymphocytes. The tumor killing ability measurement revealedthat the highest tumor cell kill was observed at the highest T lymphocyte/U-87MG ratio (100/1) and not the smaller ratios (50/1, 25/1, 10/1, and3/1), following coculture of therapeutic T lymphocytes and U-87 MGon a TCP (Figure 6). The same ratio of T cellsto U-87 MG cells of 100/1 was also applied to Mock as a positive control.Therefore, the ratio of T cells to U-87 MG cells of 100/1 was selectedfor the following study.


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)

Percentage of U-87 MG tumor cell death afterT lymphocyte treatmentat various effector/target (T lymphocyte/U87) ratios (1/0, 3/1 to100/1). Mock was applied as a negative control.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Percentage of U-87 MG tumor cell death afterT lymphocyte treatmentat various effector/target (T lymphocyte/U87) ratios (1/0, 3/1 to100/1). Mock was applied as a negative control.
Mentions: To decide the ratio of T cells to U-87 MG cellsfor optimized tumor cell death, different amounts of T lymphocyteswere added 2 h after 1 × 104 U-87 MG cells had beenseeded. AlamarBlue was used to quantify the number of viable U-87MG cells, which was quantified by AlamarBlue after T lymphocytes wereadded for 24 h and each well was washed thrice with PBS to ensureno residual T lymphocytes. The tumor killing ability measurement revealedthat the highest tumor cell kill was observed at the highest T lymphocyte/U-87MG ratio (100/1) and not the smaller ratios (50/1, 25/1, 10/1, and3/1), following coculture of therapeutic T lymphocytes and U-87 MGon a TCP (Figure 6). The same ratio of T cellsto U-87 MG cells of 100/1 was also applied to Mock as a positive control.Therefore, the ratio of T cells to U-87 MG cells of 100/1 was selectedfor the following study.

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