Phan Vy, Errington Fiona, Cheong S Chiat, Kottke Tim, Gough Michael, Altmann Sharon, Brandenburger Annick, Emery Steve, Strome Scott, Bateman Andrew, Bonnotte Bernard, Melcher Alan, Vile Richard
Molecular Medicine Program, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Nat Med. 2003 Sep;9(9):1215-9. doi: 10.1038/nm923. Epub 2003 Aug 17.
Fusion of tumor cells with antigen-presenting cells (APCs) has been proposed for the preparation of cancer vaccines. However, generation of these hybrids, using physical or chemical methods such as electrofusion or polyethylene glycol (PEG), has been difficult to standardize. Characterization of cell fusion has also been problematic because of difficulties in differentiating fusion from cell aggregation, leakage of cellular dyes and dendritic-cell (DC) phagocytosis of tumor material. In this report, we describe a new method to generate hybrid cell vaccines, based on gene transfer of a viral fusogenic membrane glycoprotein (FMG) into tumor cells, and incorporate a genetic method by which true hybrid formation can be unambiguously detected. We describe a new class of tumor cell-DC hybrid that can be rapidly isolated after cell fusion. These hybrids are highly potent in in vitro antigen presentation assays, target lymph nodes in vivo and are powerful immunogens against established metastatic disease.
有人提出将肿瘤细胞与抗原呈递细胞（APC）融合来制备癌症疫苗。然而，使用电融合或聚乙二醇（PEG）等物理或化学方法生成这些杂种细胞一直难以标准化。由于难以区分融合与细胞聚集、细胞染料泄漏以及树突状细胞（DC）对肿瘤物质的吞噬作用，细胞融合的表征也存在问题。在本报告中，我们描述了一种基于将病毒融合膜糖蛋白（FMG）基因转移到肿瘤细胞中来生成杂交细胞疫苗的新方法，并纳入了一种能够明确检测真正杂种细胞形成的遗传方法。我们描述了一类新型的肿瘤细胞-DC杂种细胞，其在细胞融合后可快速分离。这些杂种细胞在体外抗原呈递试验中效力极高，在体内靶向淋巴结，并且是针对已建立的转移性疾病的强大免疫原。
