A new genetic method to generate and isolate small, short-lived but highly potent dendritic cell-tumor cell hybrid vaccines.
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.
Phan
Vy
V
Molecular Medicine Program, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Errington
Fiona
F
Cheong
S Chiat
SC
Kottke
Tim
T
Gough
Michael
M
Altmann
Sharon
S
Brandenburger
Annick
A
Emery
Steve
S
Strome
Scott
S
Bateman
Andrew
A
Bonnotte
Bernard
B
Melcher
Alan
A
Vile
Richard
R
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D011948:Receptors, Antigen, T-Cell