Broadened clinical utility of gene gun-mediated, granulocyte-macrophage colony-stimulating factor cDNA-based tumor cell vaccines as demonstrated with a mouse myeloma model.
Broadened clinical utility of gene gun-mediated, granulocyte-macrophage colony-stimulating factor cDNA-based tumor cell vaccines as demonstrated with a mouse myeloma model.
复制标题
小鼠骨髓瘤模型证明，基因枪介导的、基于粒细胞-巨噬细胞集落刺激因子 cDNA 的肿瘤细胞疫苗的临床用途得到了扩展。
DOI：
10.1089/hum.1998.9.8-1121
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Yu,H
中科院分区：
文献类型：
--
作者：
Turner,JG;Tan,J;Crucian,BE;Sullivan,DM;Ballester,OF;Dalton,WS;Yang,NS;Burkholder,JK;Yu,H
已经描述了通过非病毒方法对小鼠B16黑色素瘤的有效免疫，其中使用基因枪将GM-CSF cDNA转移到肿瘤细胞中。我们通过使用免疫原性差的小鼠骨髓瘤MPC 11模型扩展了这种非病毒方法。用转染的、表达GM-CSF的MPC 11细胞接种疫苗在大多数试验小鼠中诱导了与肿瘤排斥相关的强效抗肿瘤细胞毒性T淋巴细胞应答。此外，近100%（28只中的27只）的无肿瘤小鼠能够拒绝肿瘤再激发。虽然这种方法由于最小的组织操作/培养和不存在感染因子而在临床上有吸引力，但许多测试的人原发性肿瘤，包括骨髓瘤细胞，在基因枪转染后未能产生高水平的GM-CSF。为了避免某些人肿瘤细胞中的低转染效率，我们表明将提供肿瘤抗原的经辐照的肿瘤细胞与基因枪转染的成纤维细胞组合以提供GM-CSF诱导的有效肿瘤排斥。我们还报道了用基因枪转染的正常人皮肤成纤维细胞产生高水平的人GM-CSF（250 ng/106 cells/24 hr）。这些结果表明，将辐照的肿瘤细胞与基因枪转染的成纤维细胞相结合会产生抗肿瘤免疫反应，并可能使这种方法更广泛地应用于癌症免疫治疗。
Effective immunization against the murine B16 melanoma by a nonviral approach in which a gene gun is used to transfer GM-CSF cDNA into tumor cells has been described. We have extended this nonviral approach by using the poorly immunogenic murine myeloma MPC11 model. Vaccination with the transfected, GM-CSF-expressing MPC11 cells induced a potent antitumor cytotoxic T lymphocyte response associated with tumor rejection in the majority of the test mice. Furthermore, nearly 100% (27 of 28) of the tumor-free mice were able to reject a tumor rechallenge. While this approach is clinically attractive because of minimal tissue manipulation/culturing and the absence of infectious agents, a number of tested human primary tumors, including myeloma cells, have failed to produce high levels of GM-CSF after gene gun transfection. To circumvent the low transfection efficiency in certain human tumor cells, we showed that combining irradiated tumor cells to provide tumor antigens together with gene gun-transfected fibroblasts to provide GM-CSF induced effective tumor rejection. We also report that normal human skin fibroblasts transfected by the gene gun produce high levels of human GM-CSF (250 ng/106cells/24 hr). These results suggest that combining irradiated tumor cells with gene gun-transfected fibroblasts results in antitumor immune responses and may allow for a wider application of this approach to cancer immunotherapy.