Tsao Ching-Ting, Kievit Forrest M, Ravanpay Ali, Erickson Ariane E, Jensen Michael C, Ellenbogen Richard G, Zhang Miqin
Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
Biomacromolecules. 2014 Jul 14;15(7):2656-62. doi: 10.1021/bm500502n. Epub 2014 Jun 25.
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.
胶质母细胞瘤患者的预后仍然很差，因为肿瘤总是在切除腔2厘米范围内复发。局部免疫疗法有潜力根除这些肿瘤的残留浸润成分。在此，我们报告了一种可生物降解水凝胶的研发情况，该水凝胶含有治疗性T淋巴细胞，用于向胶质母细胞瘤细胞进行局部递送以进行脑肿瘤免疫治疗。对热可逆聚（乙二醇）-g-壳聚糖水凝胶（PC凝胶）进行了优化，以实现T淋巴细胞的稳定释放。核磁共振光谱证实了聚（乙二醇）-g-壳聚糖的化学结构，流变学研究表明PC凝胶的溶胶-凝胶转变发生在≥32°C左右。在体外评估了T淋巴细胞通过PC凝胶的侵袭以及随后对胶质母细胞瘤的细胞毒性。结果表明PC凝胶与T淋巴细胞具有细胞相容性，并且T淋巴细胞在被包裹在PC凝胶中后仍保留其抗胶质母细胞瘤活性。PC凝胶中的T淋巴细胞在杀死胶质母细胞瘤方面比基质胶对照组中的T淋巴细胞更有效。这可能归因于PC凝胶的最佳孔径，使其能更好地让T淋巴细胞侵袭。我们的研究表明，这种独特的PC凝胶贮库可能为胶质母细胞瘤的局部免疫治疗提供一种可行的方法。
