title: A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines.
abstract: 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.
authors.affiliation: Molecular Medicine Program, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Vy
authors.initials: V
authors.lastname: Phan
authors.forename: Fiona
authors.initials: F
authors.lastname: Errington
authors.forename: S Chiat
authors.initials: SC
authors.lastname: Cheong
authors.forename: Tim
authors.initials: T
authors.lastname: Kottke
authors.forename: Michael
authors.initials: M
authors.lastname: Gough
authors.forename: Sharon
authors.initials: S
authors.lastname: Altmann
authors.forename: Annick
authors.initials: A
authors.lastname: Brandenburger
authors.forename: Steve
authors.initials: S
authors.lastname: Emery
authors.forename: Scott
authors.initials: S
authors.lastname: Strome
authors.forename: Andrew
authors.initials: A
authors.lastname: Bateman
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
authors.forename: Alan
authors.initials: A
authors.lastname: Melcher
authors.forename: Richard
authors.initials: R
authors.lastname: Vile
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D002459:Cell Fusion / Q000379:methods; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D005821:Genetic Techniques; D006023:Glycoproteins / Q000235:genetics; D006822:Hybrid Cells; D008198:Lymph Nodes / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D011948:Receptors, Antigen, T-Cell