Visted T, Bjerkvig R, Enger P O
Department of Anatomy and Cell Biology, University of Bergen, Norway.
Neuro Oncol. 2001 Jul;3(3):201-10. doi: 10.1093/neuonc/3.3.201.
Gene therapy using viral vectors has to date failed to reveal its definitive clinical usefulness. Cell encapsulation technology represents an alternative, nonviral approach for the delivery of biologically active compounds to tumors. This strategy involves the use of genetically engineered producer cells that secrete a protein with therapeutic potential. The cells are encapsulated in an immunoisolating material that makes them suitable for transplantation. The capsules, or bioreactors, permit the release of recombinant proteins that may assert their effects in the tumor microenvironment. During the last decades, there has been significant progress in the development of encapsulation technologies that comprise devices for both macro- and microencapsulation. The polysaccharide alginate is the most commonly used material for cell encapsulation and is well tolerated by various tissues. A wide spectrum of cells and tissues has been encapsulated and implanted, both in animals and humans, indicating the general applicability of this approach for both research and medical purposes, including CNS malignancies. Gliomas most frequently recur at the resection site. To provide local and sustained drug delivery, the bioreactors can be implanted in the brain parenchyma or in the ventricular system. The development of comprehensive analyses of geno- and phenotypic profiles of a tumor (genomics and proteomics) may provide new and important guidelines for choosing the optimal combination of bioreactors and recombinant proteins for therapeutic use.
迄今为止,使用病毒载体的基因治疗尚未展现出其明确的临床实用性。细胞封装技术代表了一种将生物活性化合物递送至肿瘤的非病毒替代方法。该策略涉及使用经基因工程改造的生产细胞,这些细胞可分泌具有治疗潜力的蛋白质。细胞被封装在一种免疫隔离材料中,使其适合移植。这些胶囊或生物反应器允许重组蛋白释放,而这些重组蛋白可能在肿瘤微环境中发挥作用。在过去几十年中,封装技术的发展取得了显著进展,这些技术包括用于宏观和微观封装的装置。多糖藻酸盐是细胞封装最常用的材料,并且能被各种组织良好耐受。在动物和人类中,已有多种细胞和组织被封装并植入,这表明该方法在包括中枢神经系统恶性肿瘤在内的研究和医学目的方面具有普遍适用性。胶质瘤最常于切除部位复发。为了实现局部和持续的药物递送,生物反应器可植入脑实质或脑室系统。对肿瘤的基因和表型谱进行全面分析(基因组学和蛋白质组学)的发展,可能为选择用于治疗的生物反应器和重组蛋白的最佳组合提供新的重要指导方针。