A generic RNA-pulsed dendritic cell vaccine strategy for renal cell carcinoma

Journal of Translational Medicine

Dolores J Schendel²  Elfriede Noessner²  Andreas Weinzierl¹  Sybille Regn²  Christiane Geiger² 

[1]Institute of Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany

[2]Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munich, Germany

关键词: immunotherapy;    tumor vaccine;    renal cell carcinoma;    tumor-derived RNA;    dendritic cells;   

Others  :  1208487
DOI  :  10.1186/1479-5876-3-29

 received in 2005-05-11, accepted in 2005-07-26,  发布年份 2005

【 摘 要 】

We present a generic dendritic cell (DC) vaccine strategy for patients with renal cell carcinoma (RCC) based on the use of RNA as a source of multiplex tumor-associated antigens (TAAs). Instead of preparing RNA from tumor tissue of each individual RCC patient, we propose to substitute RNA prepared from a well characterized highly immunogenic RCC cell line (RCC-26 tumor cells) as a generic source of TAAs for loading of DCs. We demonstrate here that efficient RNA transfer can be achieved using lipofection of immature DCs, which are subsequently matured with a cytokine cocktail to express high levels of MHC and costimulatory molecules as well as the chemokine receptor CCR7. Neither RNA itself nor the lipid component impacted on the phenotype or the cytokine secretion of mature DCs.

Following RNA loading, DCs derived from HLA-A2-positive donors were able to activate effector-memory cytotoxic T lymphocytes (CTLs) specific for a TAA ligand expressed by the RCC-26 cell line. CTL responses to RNA-loaded DCs reached levels comparable to those stimulated directly by the RCC-26 tumor cells. Furthermore, DCs expressing tumor cell RNA primed naïve T cells, yielding T cell lines with cytotoxicity and cytokine secretion after contact with RCC tumor cells. RCC-26 cell lines are available as good manufacturing practice (GMP)-certified reagents enabling this source of RNA to be easily standardized and adapted for clinical testing. In addition, well defined immune monitoring tools, including the use of RNA expressing B cell lines, are available. Thus, this DC vaccine strategy can be directly compared with an ongoing gene therapy trial using genetically-engineered variants of the RCC-26 cell line as vaccines for RCC patients with metastatic disease.

【 授权许可】

   
2005 Geiger et al; licensee BioMed Central Ltd.

【 图 表 】

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