Nature Medicine
9, 1215 - 1219 (2003)
Published online: 17 August 2003; | doi:10.1038/nm923
A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccinesVy Phan1, Fiona Errington2, S Chiat Cheong3, Tim Kottke1, Michael Gough1, Sharon Altmann1, Annick Brandenburger3, Steve Emery4, Scott Strome5, Andrew Bateman1, Bernard Bonnotte6, Alan Melcher2
& Richard Vile1, 71
Molecular Medicine Program, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. 2
CRUK Oncology Unit, St. James' Hospital, Leeds LS9 7TF, UK. 3
Université Libre de Bruxelles, 6041 Gosselies, Belgium. 4
AstraZeneca, Alderley Park, Cheshire, SK10, UK. 5
Department of Otorhinolaryngology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. 6
INSERM U517, Faculty of Medicine, 21079 Dijon Cedex, France. 7
Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Correspondence should be addressed to Richard Vile vile.richard@mayo.eduFusion 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.
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