Fujiwara T, Grimm E A, Roth J A
Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston 77030.
Curr Opin Oncol. 1994 Jan;6(1):96-105. doi: 10.1097/00001622-199401000-00014.
Recent advances in molecular biology have opened new avenues of basic genetic engineering technology and have made possible the application of this technology in clinical human gene therapy. Replication-defective viral vectors and biocompatible materials, eg, liposomes, have been developed as vehicles to introduce potentially therapeutic genes into mammalian cells. Over the past 2 years, this technology has increased the possibilities for therapy in numerous genetic diseases. Approaches at the molecular level have also demonstrated that one of the mechanisms of human cancer development is overexpression of dominant oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or mutations that induce inactivation of tumor-suppressor activity. This concept suggests that the introduction of antisense oncogenes and wild-type tumor-suppressor genes, eg, p53, could halt or reverse these mechanisms, thus having a therapeutic effect in cancer. Moreover, evidence that the immune system is capable of eliminating tumor cells in numerous animal models has suggested gene therapy approaches for the delivery of cytokines, which promote the activation of cytotoxic immune responses against the malignant tissue. The efficacy of these gene therapy protocols is now being evaluated in both animal model systems and clinical trials. This article reviews recent highlights in this rapidly evolving field.
分子生物学的最新进展为基础基因工程技术开辟了新途径，并使该技术在临床人类基因治疗中的应用成为可能。复制缺陷型病毒载体和生物相容性材料，如脂质体，已被开发为将潜在治疗性基因导入哺乳动物细胞的载体。在过去两年中，这项技术增加了治疗多种遗传疾病的可能性。分子水平的研究方法还表明，人类癌症发展的机制之一是显性癌基因的过度表达、突变癌基因的表达，或导致肿瘤抑制活性失活的特定染色体缺失或突变。这一概念表明，引入反义癌基因和野生型肿瘤抑制基因，如p53，可能会阻止或逆转这些机制，从而对癌症产生治疗作用。此外，在众多动物模型中免疫系统能够消除肿瘤细胞的证据提示了通过基因治疗递送细胞因子的方法，这些细胞因子可促进针对恶性组织的细胞毒性免疫反应的激活。目前正在动物模型系统和临床试验中评估这些基因治疗方案的疗效。本文综述了这一快速发展领域的最新亮点。
