Tumour cell-dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocols.
BACKGROUND
Fusion of tumour cells with dendritic cells (DC) is a powerful new technology to increase tumour vaccine immunogenicity. The aim of this study was to compare fusion protocols with syngenic DCs with respect to the efficiency of polyethylen-glycol-(PEG) and electric pulse-mediated fusions for induction of protective anti-tumour immune responses. As a model we chose a low immunogenic and metastatic murine mammary carcinoma cell line, which mimics clinically relevant tumour features.


METHODS
FACS-staining, chromium release assay, therapeutic immunization, adoptive transfer.


RESULTS
We show that the parental line with low cell surface expression of MHC molecules as well as a lacZ transfectant becomes highly immunogenic upon fusion with DCs. This was true for PEG- as well as for electro-fused cells. Immunization with products of DCs and tumour cells cocultivated for 16 h without the fusing agent PEG also caused induction of profound anti-tumour immunity, while this was not the case when using parental tumour cells or their lacZ transfectants as vaccines. Immune protection against the parental tumour cells after vaccination with fused cells was long-lasting and could be transferred via immune spleen cells into immuno-incompetent nude (nu/nu) mice.


CONCLUSIONS
Fusion products of DA3(hi) mammary carcinoma cells and DCs produced by an electric pulse were similar to those produced by PEG fusion with regard to vaccine potency in prophylactic antitumour immunization assays in vivo. Therefore, both techniques seem to be promising for clinical application.
Lindner
Matthias
M
University Hospital for Gynecology and Obstetrics, Voss-Strasse 9, 69115 Heidelberg, Germany. matthias_lindner@med.uni-heidelberg.de
Schirrmacher
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000494:pharmacology*; D002459:Cell Fusion / Q000379:methods*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D018274:Electroporation; D015870:Gene Expression / Q000187:drug effects; D007121:Immunocompetence; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000494:pharmacology; D007763:Lac Operon; D008285:Major Histocompatibility Complex / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D016513:Mice, SCID; D011092:Polyethylene Glycols; D001616:beta-Galactosidase / Q000235:genetics
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D001616:beta-Galactosidase