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Published on: May 27, 2011
Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells
Frank Grünebach1, Stefanie Erndt, Maik Häntschel
1Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
Abstract:
Advances in tumor immunology and Identification of tumor-associated antigens (TAAs) provide a basis for the development of novel immunotherapies to treat malignant diseases. In order to identify novel TAAs, we performed comparative microarray analysis of (heterogeneous) tissues and found regulator of G protein-signaling 1 (RGS1) extensively up-regulated in renal cell carcinoma (RCC) tissues. To examine the possible function of this molecule as a novel, broadly applicable TAA, synthetic full-length RGS1-mRNA was synthesized for the transfection of monocyte-derived dendritic cells (DCs). These modified antigen-presenting cells (APCs) were then used to induce RGS1-specific cytotoxic T cells (CTLs) in vitro. The CTLs generated from several healthy donors and a patient with chronic lymphocytic leukemia (CLL) elicited an antigen-specific and HLA-A2- and -A3-restricted cytolytic activity against tumor cells endogenously expressing the RGS1 protein including renal cell carcinomas (RCCs), melanoma, ovarian carcinoma and the primary autologous CLL-blasts. In conclusion, our study demonstrates that the in vitro induction of RGS1-specific CTLs by RNA-transfected DCs is feasible and highly effective. Since this molecule is (over-) expressed in a broad variety of malignancies it might represent an interesting novel TAA in the context of cancer vaccines designed to target RGS1 expressing tumor cells.
Insights
Researchers identified Regulator of G protein-signaling 1 (RGS1) as a promising tumor-associated antigen (TAA). RGS1-specific T-cells were effectively generated in vitro, showing potential for novel cancer immunotherapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor immunology advances enable novel cancer immunotherapies.
- Identifying tumor-associated antigens (TAAs) is crucial for targeted treatments.
Purpose of the Study:
- To identify novel TAAs for cancer immunotherapy.
- To investigate the potential of Regulator of G protein-signaling 1 (RGS1) as a TAA.
Main Methods:
- Comparative microarray analysis identified RGS1 upregulation in renal cell carcinoma (RCC).
- Synthetic RGS1 mRNA was used to transfect dendritic cells (DCs).
- RGS1-specific cytotoxic T lymphocytes (CTLs) were generated in vitro using modified antigen-presenting cells (APCs).
Main Results:
- RGS1 was found to be extensively upregulated in RCC tissues.
- In vitro generated RGS1-specific CTLs demonstrated antigen-specific, HLA-restricted cytolytic activity.
- Target tumor cells included RCC, melanoma, ovarian carcinoma, and chronic lymphocytic leukemia (CLL) blasts.
Conclusions:
- In vitro induction of RGS1-specific CTLs by RNA-transfected DCs is feasible and effective.
- RGS1's broad expression across malignancies suggests its potential as a novel TAA.
- RGS1 may be a valuable target for cancer vaccines against RGS1-expressing tumors.
