Transfection of dendritic cells (DCs) with the CIITA gene: increase in immunostimulatory activity of DCs
| Autor: | Peter Buttgereit, Angela Märten, Frank Schakowski, A Allera, Sabine Renoth, Ingo G.H. Schmidt-Wolf, S König, Tilman Sauerbruch, Carsten Ziske, A. von Rücker, Burghardt Wittig, Silvia Weineck, Björn Schöttker, Roland Schroers |
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| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Cancer Research animal structures viruses Genes MHC Class II Genetic Vectors CIITA Gene Priming (immunology) chemical and pharmacologic phenomena Ligands Transfection Adenoviridae MHC Class II Gene Antigen Tumor Cells Cultured CIITA Humans Polylysine Molecular Biology MHC class II biology Reverse Transcriptase Polymerase Chain Reaction Chemistry Effector Carcinoma fungi Nuclear Proteins Dendritic Cells Cell biology Pancreatic Neoplasms Gene Expression Regulation Colonic Neoplasms embryonic structures Immunology Trans-Activators biology.protein Molecular Medicine Immunization |
| Zdroj: | Cancer Gene Therapy. 8:211-219 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700292 |
| Popis: | Dendritic cells (DCs) are the major antigen-presenting cells. They are able to present tumor antigens to immunologic effector cells. MHC class II molecules on DC surfaces play an important role in priming effector cells against tumor cells and their antigens. The transactivator CIITA (MHC class II transactivator) is a non-DNA-binding transactivator, which regulates the expression of MHC class II, HLA-DM, and invariant chain and behaves as a master controller of constitutive and inducible MHC class II gene activation. Here, we transfected DCs with the CIITA gene using a novel transfection technique. The vector system consisted of a plasmid bound to an adenovirus via poly-L-lysine, which is covalently bound to a UV-irradiated adenovirus. After transfection, expression of MHC class II on DCs increased from 27% to 75% on day 2 after transfection. Transfected DCs were co-cultured with immunologic effector cells. Cytotoxicity of effector cells against tumor cells increased after co-culture with transfected DCs to 63% compared to 15% with effector cells co-cultured with irrelevantly transfected DCs (P=.037). This effect was dependent on the timing and period of co-culture. In conclusion, transfection of DCs led to an increase in antitumoral immunostimulatory capacity of DCs. We can further conclude that DCs could be efficiently transfected with the CIITA gene. Transfection of DCs led to an increase in antitumoral immunostimulatory capacity of DCs and may have a major impact on immunotherapeutic protocols for patients with cancer. |
| Databáze: | OpenAIRE |
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