Increase of in vivo antitumoral activity by CD40L (CD154) gene transfer into pancreatic tumor cell-dendritic cell hybrids.
OBJECTIVE
Fusion of dendritic cells (DC) with tumor cells is an approach in immunotherapy combining antigenicity and capacity of antigen presentation to activate T cells for the induction of tumor-specific cytotoxic immunity. Although there have been reports of clinical benefit, response rates have been limited and further improvements are warranted.


METHODS
We used murine DC and a novel protocol for an effective fusion of those cells with the murine pancreatic cell line Panc02.


RESULTS
We observed 2 events: only moderate in vitro and in vivo cytotoxicity of tumor cell/DC hybrids and a down-regulation of costimulatory molecules on fused cells. Therefore, we transfected tumor cell/DC hybrids with an adenovirus expressing CD154 to improve DC activation and generating antitumor immune response without the need of CD4 T cells. High CD154 expression could be obtained by transfection of DC and Panc02 cells prior fusion. Furthermore, vaccination with CD154-transfected tumor cell/DC hybrid led to a significantly increased induction of cytotoxic T cells in vitro and to an improved antitumoral effect in an orthotopic in vivo mouse model.


CONCLUSIONS
CD154-transfected tumor cell/DC hybrids are a promising approach to increase the efficiency of antitumoral response.
Ziske
Carsten
C
Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Etzrodt
Patricia E
PE
Eliu
Alex-S
AS
Gorschlüter
Marcus
M
Strehl
John
J
Flieger
Dimitri
D
Messmer
Davorka
D
Schmitz
Volker
V
Gonzalez-Carmona
Maria A
MA
Sievers
Elisabeth
E
Brossart
Peter
P
Sauerbruch
Tilman
T
Schmidt-Wolf
Ingo G H
IG
D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006822:Hybrid Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D023201:CD40 Ligand