Jaffee E M, Dranoff G, Cohen L K, Hauda K M, Clift S, Marshall F F, Mulligan R C, Pardoll D M
Departments of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Cancer Res. 1993 May 15;53(10 Suppl):2221-6.
Preclinical studies with murine tumor models have demonstrated that autologous tumor cell vaccines engineered to secrete certain cytokines in a paracrine fashion elicit systemic immune responses capable of eliminating small amounts of established tumor. These results have engendered much interest in developing this strategy for gene therapy of human cancer. The major limitation to creating genetically modified autologous human tumor vaccines is efficient gene transfer into primary tumor explants, since the majority of human tumors fail to proliferate in long-term culture. Using the retroviral vector MFG in conjunction with short-term culture techniques, we have achieved, in the absence of selection, a mean transduction efficiency of 60% in primary renal, ovarian, and pancreatic tumor explants, and we have developed an autologous granulocyte-macrophage colony-stimulating factor secreting tumor vaccine for clinical trials.
对鼠类肿瘤模型的临床前研究表明，经工程改造以旁分泌方式分泌某些细胞因子的自体肿瘤细胞疫苗可引发全身免疫反应，能够消除少量已形成的肿瘤。这些结果引发了人们对开发这种人类癌症基因治疗策略的浓厚兴趣。创建基因改造的自体人类肿瘤疫苗的主要限制在于将基因有效转移到原发性肿瘤外植体中，因为大多数人类肿瘤在长期培养中无法增殖。通过将逆转录病毒载体MFG与短期培养技术结合使用，我们在无选择的情况下，在原发性肾、卵巢和胰腺肿瘤外植体中实现了平均60%的转导效率，并且我们已经开发出一种用于临床试验的自体分泌粒细胞-巨噬细胞集落刺激因子的肿瘤疫苗。
