Targeting of melanoma brain metastases using engineered neural stem/progenitor cells
Targeting of melanoma brain metastases using engineered neural stem/progenitor cells
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DOI：
10.1215/15228517-2005-012
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发表时间：
2006-04-01
期刊：
影响因子：
15.9
通讯作者：
Perides, G
中科院分区：
文献类型：
--
作者：
Aboody, KS;Najbauer, J;Perides, G
对于癌症患者，尤其是晚期黑色素瘤患者来说，脑转移是一个日益常见和严重的临床问题。鉴于神经干/祖细胞 (NSPC) 对中枢神经系统病理区域的广泛趋向性，我们扩大了研究范围，以确定 NSPC 是否也可以在同基因实验黑色素瘤模型中靶向脑转移的多个部位。使用表达胞嘧啶脱氨酶的 NSPC (CD-NSPC) 和全身性 5-氟胞嘧啶 (5-FC) 前药给药，我们探索了它们作为基于细胞的靶向药物递送系统治疗播散性脑转移瘤的潜力。我们的结果表明 NSPC 对脑内黑色素瘤转移有很强的趋向性。此外，在我们的治疗范例中，已确定黑色素瘤脑转移的动物接受了 CD-NSPC 的颅内植入，然后进行全身 5-FC 治疗，导致肿瘤负荷显着（71％）减少。这些数据为使用 NSPC 将治疗基因产物靶向递送至黑色素瘤脑转移提供了原理证明。
Brain metastases are an increasingly frequent and serious clinical problem for cancer patients, especially those with advanced melanoma. Given the extensive tropism of neural stem/progenitor cells (NSPCs) for pathological areas in the central nervous system, we expanded investigations to determine whether NSPCs could also target multiple sites of brain metastases In a syngeneic experimental melanoma model. Using cytosine deaminase-expressing NSPCs (CD-NSPCs) and systemic 5-fluorocytosine (5-FC) pro-drug administration, we explored their potential as a cell-based targeted drug delivery system to disseminated brain metastases. Our results indicate a strong tropism of NSPCs for intracerebral melanoma metastases. Furthermore, in our therapeutic paradigm, animals with established melanoma brain metastasis received intracranial implantation of CD-NSPCs followed by systemic 5-FC treatment, resulting in a significant (71%) reduction in tumor burden. These data provide proof of principle for the use of NSPCs for targeted delivery of therapeutic gene products to melanoma brain metastases.