Transfected human dendritic cells to induce antitumor immunity.
Dendritic cells are professional antigen-presenting cells able to prime naive T lymphocytes and regulate steadily the delicate balance between tolerance and activation during the immune response. In past years several reports have shown that genetically engineered dendritic cells (DCs) can be a powerful tool for inducing an antigen-specific immune response. The use of such modified antigen-presenting cells is a real working hypothesis in preclinical studies and in clinical vaccination approaches for cancer treatment. The definition of optimal transfection conditions for preserving DC survival and functionality is necessary to design a correct immunotherapeutic protocol. Different lipid-based transfection compounds were studied for their effects on DC survival, phenotype and functional properties. All the transfection procedures were able to select DCs with a higher expression of activation and costimulatory molecules (ie MHCII-DR, CD83, CD86, CD25) than the untreated DCs. However, only two compounds (LipofectAMINE PLUS and FuGENE 6), preserved or even increased the immunopotency of DCs as antigen-presenting cells. These protocols were applied to modify DCs in order to express an epithelial tumor-associated antigen, MUC1, and such cells were able to induce in vitro a specific immune response in healthy donors.
Rughetti
A
A
Department of Experimental Medicine and Pathology, Università di Roma La Sapienza, Italy.
Biffoni
M
M
Sabbatucci
M
M
Rahimi
H
H
Pellicciotta
I
I
Fattorossi
A
A
Pierelli
L
L
Scambia
G
G
Lavitrano
M
M
Frati
L
L
Nuti
M
M
D019496:Cancer Vaccines; D002411:Cation Exchange Resins; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D000939:Epitopes / Q000235:genetics; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids; D008081:Liposomes; D008213:Lymphocyte Activation; D018396:Mucin-1 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods*
D019496:Cancer Vaccines; D002411:Cation Exchange Resins; D000939:Epitopes; C411955:FuGene; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D018396:Mucin-1; D012333:RNA, Messenger