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.
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.
Authors: Xi Zhao; Anamika Bose; Hideo Komita; Jennifer L Taylor; Mayumi Kawabe; Nina Chi; Laima Spokas; Devin B Lowe; Christina Goldbach; Sean Alber; Simon C Watkins; Lisa H Butterfield; Pawel Kalinski; John M Kirkwood; Walter J Storkus Journal: Mol Ther Date: 2010-12-28 Impact factor: 11.454
Authors: Barbara Seliger; Sven P Dressler; Chiara Massa; Christian V Recktenwald; Florian Altenberend; Juergen Bukur; Francesco M Marincola; Ena Wang; Stefan Stevanovic; Rudolf Lichtenfels Journal: Proteomics Date: 2011-05-18 Impact factor: 3.984
Authors: Rebecca A Roof; Katarzyna Sobczyk-Kojiro; Anjanette J Turbiak; David L Roman; Irina D Pogozheva; Levi L Blazer; Richard R Neubig; Henry I Mosberg Journal: Chem Biol Drug Des Date: 2008-07-15 Impact factor: 2.817
Authors: Martin A Cheever; James P Allison; Andrea S Ferris; Olivera J Finn; Benjamin M Hastings; Toby T Hecht; Ira Mellman; Sheila A Prindiville; Jaye L Viner; Louis M Weiner; Lynn M Matrisian Journal: Clin Cancer Res Date: 2009-09-01 Impact factor: 12.531