Pardoll D
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Curr Opin Oncol. 1992 Dec;4(6):1124-9. doi: 10.1097/00001622-199212000-00018.
Recently, new tumor vaccine approaches were developed in animal systems that modify tumor cells genetically to secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigens or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. The development of high efficiency gene transfer technologies such as defective retroviral vectors allows for the translation of these preclinical studies to clinical trials. However, before large investments are made in this area of gene therapy, it will be important to demonstrate that the actual gene transfer component of the strategy significantly enhances antitumor immune responses relative to alternative nongenetic approaches.
最近，在动物系统中开发了新的肿瘤疫苗方法，即通过基因改造肿瘤细胞以分泌某些细胞因子。对肿瘤细胞进行工程改造使其以旁分泌方式分泌细胞因子，可诱导强大的局部细胞因子效应，而不会产生明显的全身毒性。除了局部炎症外，这种方法还可以改变肿瘤抗原的呈递或激活肿瘤抗原特异性T淋巴细胞，从而产生全身抗肿瘤免疫。诸如缺陷逆转录病毒载体等高效基因转移技术的发展，使得这些临床前研究能够转化为临床试验。然而，在对该基因治疗领域进行大量投资之前，重要的是要证明该策略中实际的基因转移成分相对于其他非基因方法能显著增强抗肿瘤免疫反应。
