Identification and characterization of T-cell epitopes deduced from RGS5, a novel broadly expressed tumor antigen.
OBJECTIVE
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.


METHODS
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.
Boss
Cristina N
CN
Department of Oncology, University of Tübingen, Tübingen, Germany.
Grünebach
Frank
F
Brauer
Katharina
K
Häntschel
Maik
M
Mirakaj
Valbona
V
Weinschenk
Toni
T
Stevanovic
Stefan
S
Rammensee
Hans-Georg
HG
Brossart
Peter
P
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D015789:HLA-A2 Antigen / Q000737:chemistry; D015791:HLA-A3 Antigen / Q000737:chemistry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D020710:RGS Proteins / Q000096:biosynthesis* / Q000276:immunology*; D012334:RNA, Neoplasm / Q000378:metabolism
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010455:Peptides; D020710:RGS Proteins; C491349:RGS5 protein, human; D012334:RNA, Neoplasm