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Identification and Characterization of T-Cell Epitopes Deduced from RGS5, a Novel Broadly Expressed Tumor Antigen

Authors' Affiliations: ¹ Department of Oncology, Hematology, Immunology, Rheumatology, and Pulmology and ² Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

Requests for reprints: Peter Brossart, Department of Internal Medicine II, Oncology, Hematology, Immunology, Rheumatology, and Pulmology, University of Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. Phone: 49-7071/29 -82726; Fax: 49-7071/29-5709; E-mail: peter.brossart{at}med.uni-tuebingen.de.

Purpose: Identification of tumor-associated antigens and advances in tumor immunology resulted in the development of vaccination strategies to treat patients with malignant diseases. In a novel experimental approach that combined comparative mRNA expression analysis of defined cell types with the characterization of MHC ligands by mass spectrometry, we found that regulator of G protein signaling 5 (RGS5) is extensively up-regulated in a broad variety of malignant cells, and we identified two HLA-A2– and HLA-A3–binding peptides derived from the RGS5 protein. Interestingly, RGS5 was recently shown to be involved in tumor angiogenesis.

Experimental Design: We used monocyte-derived dendritic cells pulsed with these novel antigenic peptides or transfected with RGS5-mRNA for the in vitro induction of CTLs, generated from healthy donors, to analyze the presentation of RGS5-deduced epitopes by malignant cells.

Results: The generated CTL lines elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the RGS5 protein. Furthermore, we were able to induce RGS5-specific CTLs using peripheral blood mononuclear cells from a patient with acute myeloid leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells.

Conclusions: These results indicate that the RGS5 peptides represent interesting candidates for the development of cancer vaccines designed to target malignant cells and tumor vessels.