Transfected human dendritic cells to induce antitumor immunity

被引:37
作者
Rughetti, A
Biffoni, M
Sabbatucci, M
Rahimi, H
Pellicciotta, I
Fattorossi, A
Pierelli, L
Scambia, G
Lavitrano, M
Frati, L
Nuti, M
机构
[1] Univ Rome La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy
[2] Catholic Univ Rome, Inst Haematol, Rome, Italy
[3] Catholic Univ Rome, Inst Gynaecol, Rome, Italy
关键词
cancer vaccine; human dendritic cells; transfection;
D O I
10.1038/sj.gt.3301266
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Ali 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.
引用
收藏
页码:1458 / 1466
页数:9
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