Kangasniemi L, Koskinen M, Jokinen M, Toriseva M, Ala-Aho R, Kähäri V-M, Jalonen H, Ylä-Herttuala S, Moilanen H, Stenman U-H, Diaconu I, Kanerva A, Pesonen S, Hakkarainen T, Hemminki A
Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory, University of Helsinki, Helsinki, Finland.
Gene Ther. 2009 Jan;16(1):103-10. doi: 10.1038/gt.2008.142. Epub 2008 Aug 28.
Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.
尽管临床前研究结果令人鼓舞，但迄今为止癌症基因治疗的临床益处并不大。主要障碍仍然是基因传递到肿瘤足够大区域的水平和持久性。克服这一问题的一种方法可能需要延长局部病毒释放。我们研究了硅胶整体柱在将腺病毒递送至晚期原位胃癌和胰腺癌肿瘤中的效用。最初，研究了二氧化硅-病毒基质的生化特性，并检测到其释放几乎呈时间的线性函数。病毒在37摄氏度下可保持感染性数周，在4摄氏度下可保持数月，这可能便于储存和分发。在体内，观察到功能性复制缺陷型以及复制能力强、衣壳修饰的溶瘤病毒的延长释放。用胰腺癌治疗小鼠可使其生存期延长一倍（P<0.001）。此外，基于硅胶的递送减缓了抗腺病毒抗体的产生。
