Silk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.
Silk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.
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DOI：
10.1002/hed.23877
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Wong RJ
中科院分区：
文献类型：
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作者：
Price DL;Li P;Chen CH;Wong D;Yu Z;Chen NG;Yu YA;Szalay AA;Cappello J;Fong Y;Wong RJ
溶瘤病毒的功效可能因病毒渗透到肿瘤中而受到限制。手术切除后立即术中应用病毒可能会增强这一效果。溶瘤痘苗病毒 GLV-1h68 在体外和体内以丝弹性蛋白样蛋白聚合物 (SELP) 的形式递送至裸鼠的未变性甲状腺癌细胞系 8505c 中。 SELP 中的 GLV-1h68 在体外感染并裂解间变性甲状腺癌细胞，其效果与磷酸盐缓冲盐水 (PBS) 中的效果相同，并且在 1 周时保留了 1000 倍以上的感染性噬斑形成单位。在残留肿瘤的手术切除模型中，与 PBS 相比，SELP 中的 GLV-1h68 改善了肿瘤控制，并显示出病毒 β-半乳糖苷酶表达增加。使用 SELP 基质进行术中溶瘤病毒递送可保护感染性病毒颗粒免于降解，促进持续的病毒递送和转基因表达，并改善肿瘤控制。溶瘤病毒递送方法的这种优化可以增强治疗效果。
Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes.