Cirone P, Saller R M, Chang P L
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Curr Pharm Biotechnol. 2001 Sep;2(3):269-77. doi: 10.2174/1389201013378680.
Immuno-isolation provides a potentially safe and effective method of delivering recombinant therapeutic molecules. Its application as a drug-delivery platform for the treatment of cancer has shown promising developments recently. This review will summarize the principle and current progress of this novel therapy paradigm in oncology. In this approach, a non-autologous cell line is genetically modified to secrete a recombinant product with potential for tumor suppression. Such a cell line may be implanted without graft rejection into all patients with similar neoplastic disease. The immune protection is conferred by enclosure within immuno-isolating devices such as microcapsules whose permeability would allow passage of smaller molecules such as oxygen, nutrients and waste products as well as the desired therapeutic transgene product. However, large immune mediators such as complement, macrophages and lymphocytes responsible for graft rejection would be excluded. In this review, we will consider how this technology may be applied as a novel genetic tool for cancer treatment to deliver antibodies, cytokines, enzymes and growth factors for treatment of various types of cancer. These molecules can be delivered at low constitutive levels, thereby permitting long-term systemic delivery, maintaining biological activity over extended periods, and eliminating the costs of product purification. The current success of this strategy in cancer treatment will be reviewed in in vitro systems, in animal models of cancer, and in human clinical trials.
免疫隔离提供了一种递送重组治疗分子的潜在安全有效的方法。其作为治疗癌症的药物递送平台的应用近来已展现出有前景的进展。本综述将总结这种肿瘤学新治疗模式的原理和当前进展。在这种方法中，一种非自体细胞系经基因改造以分泌具有肿瘤抑制潜力的重组产物。这样的细胞系可植入而不会发生移植排斥反应，适用于所有患有相似肿瘤疾病的患者。免疫保护通过封装在免疫隔离装置如微胶囊中来实现，微胶囊的通透性允许小分子如氧气、营养物质和代谢废物以及所需的治疗性转基因产物通过。然而，负责移植排斥反应的大的免疫介质如补体、巨噬细胞和淋巴细胞将被排除在外。在本综述中，我们将探讨这项技术如何作为一种用于癌症治疗的新型基因工具来递送抗体、细胞因子、酶和生长因子以治疗各种类型的癌症。这些分子可以以低组成水平递送，从而实现长期全身递送，在较长时间内维持生物活性，并消除产品纯化成本。将在体外系统、癌症动物模型和人体临床试验中综述该策略目前在癌症治疗中的成功情况。
