Vector-producing tumor-tracking multipotent mesenchymal stromal cells for suicide cancer gene therapy.
Vector-producing tumor-tracking multipotent mesenchymal stromal cells for suicide cancer gene therapy.
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DOI：
10.2741/2808
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
T. Okada;K. Ozawa
中科院分区：
文献类型：
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作者：
T. Okada;K. Ozawa
使用逆转录病毒载体生产细胞的自杀性癌症基因疗法是复发性胶质母细胞瘤手术切除术的辅助手段，尽管任何益处似乎都是微不足道的。如果载体和转基因被更有效地递送到肿瘤细胞，这种治疗方法可能会有更好的结果。我们以前已经证明，由腺病毒-逆转录病毒混合载体工程化的肿瘤细胞产生逆转录病毒后代，破坏卫星肿瘤细胞。载体产生细胞的全身递送是否可以有效地治疗侵袭性肿瘤仍有待确定。有效的逆转录病毒载体递送载体可以是多能间充质基质细胞（MSC），其已被证明在体内归巢至肿瘤细胞并以最小的宿主排斥递送癌症杀伤基因或免疫产物。因此，有可能用MSC递送的重组子代载体来治疗肿瘤。这可能特别适用于治疗弥漫性癌症，如多形性胶质母细胞瘤。虽然这种策略仍有待在各种原位或转移性肿瘤模型中进行测试，但它有可能大大改善自杀基因治疗的结果。
Suicide cancer gene therapy with retroviral vector-producing cells was in the way of an adjuvant to the surgical resection of recurrent glioblastoma, although any benefit appeared to be marginal. It is likely that this therapeutic approach may have better outcomes if the vectors and transgenes are delivered more efficiently to the tumor cells. We have shown previously that tumor cells engineered by adenovirus-retrovirus hybrid vectors to produce retroviral progeny destroy satellite tumor cells. Whether the systemic delivery of vector-producing cells can effectively treat aggressive tumors remains to be determined. Effective retroviral vector delivery vehicles may be multipotent mesenchymal stromal cells (MSCs), which have been shown to home to tumor cells in vivo and deliver cancer-killing gene or immune products with minimal host rejection. Therefore, it may be possible to transduce tumors with recombinant progeny vectors delivered by MSCs. This may be particularly suitable for treating diffuse cancers like glioblastoma multiforme. While this strategy remains to be tested in various orthotopic or metastatic tumor models, it has the potential to greatly improve the outcome of suicide gene therapy.