Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells

被引：0
作者：
Frank Grünebach
Stefanie Erndt
Maik Häntschel
Annkristin Heine
Peter Brossart
机构：
[1] University of Tübingen,Departments of Internal Medicine II, Oncology, Hematology, Immunology, Rheumatology and Pulmology
[2] University of Bonn,Department of Hematology and Oncology
来源：
Cancer Immunology, Immunotherapy | 2008年 / 57卷
关键词：
Renal Cell Carcinoma; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia Patient; RGS1 Protein;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
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页码：1483 / 1491
页数：8
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