Orentas R J, Schauer D, Bin Q, Johnson B D
Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Cell Immunol. 2001 Oct 10;213(1):4-13. doi: 10.1006/cimm.2001.1864.
The absence of surface costimulatory molecules explains in part the lack of an effective anti-tumor immune response in tumor-bearing animals, even though unique tumor antigens may be presented by class I MHC. We determined that the immunogenicity of a murine neuroblastoma, Neuro-2a, which lacks surface costimulatory molecules, could be increased by electrically induced fusion with dendritic cells. Electrofusion induced a higher level of cell fusion than polyethylene glycol, and tumor/dendritic cell heterokaryons expressed high levels of costimulatory molecules. While Neuro-2a was unable to induce the proliferation of syngeneic or allogeneic T cells in vitro, fused cells were able to induce T cell responses both in vitro and in vivo. When fused dendritic tumor cells were used as a cancer vaccine, immunized mice were significantly protected from challenge with Neuro-2a. We propose that electrofusion with patient-derived tumor and dendritic cells may provide a rapid means to produce patient-specific tumor vaccines.
表面共刺激分子的缺失部分解释了荷瘤动物缺乏有效的抗肿瘤免疫反应的原因，尽管独特的肿瘤抗原可能由I类主要组织相容性复合体（MHC）呈递。我们确定，缺乏表面共刺激分子的小鼠神经母细胞瘤Neuro-2a的免疫原性可通过与树突状细胞电诱导融合来提高。电融合诱导的细胞融合水平高于聚乙二醇，肿瘤/树突状细胞异核体表达高水平的共刺激分子。虽然Neuro-2a在体外不能诱导同基因或异基因T细胞增殖，但融合细胞在体外和体内均能诱导T细胞反应。当融合的树突状肿瘤细胞用作癌症疫苗时，免疫的小鼠能显著免受Neuro-2a攻击。我们提出，将患者来源的肿瘤细胞与树突状细胞进行电融合可能提供一种快速制备患者特异性肿瘤疫苗的方法。
