AIM-2: a novel tumor antigen is expressed and presented by human glioma cells.
Antigen isolated from Immunoselected Melanoma-2 (AIM-2) was recently identified using melanoma-reactive CD8 T cells. AIM-2 antigen is expressed in a wide variety of tumor types, including neuroectodermal tumors, as well as breast, ovarian and colon carcinomas. In this study, we analyzed AIM-2 expression in glioblastoma multiforme (GBM) in primary cultured cells and established GBM cell lines. We found that the primary GBM cell lines expressed 88.4% and 93.0% of non-spliced and spliced AIM-2, respectively. Five out of seven of the established GBM cell lines expressed both non-spliced and spliced AIM-2. Furthermore, the C9 CTL clone, which is specific for AIM-2 peptide (RSDSGQQARY), efficiently recognized GBM tumor cells in an antigen-specific and HLA-A1 restricted manner. IFN-gamma treatment of the GBM tumor cells dramatically increased HLA-A1 expression levels and, consequently, increased CTL recognition of the treated tumor cells. More importantly, seven out of 12 HLA-A1 and AIM-2 positive patients from our dendritic cell clinical trial generated AIM-2 specific CTL activity in their PBMC after vaccinations. These data indicate that AIM-2 could be used as a tumor antigen target for monitoring vaccine trials or to develop antigen specific active immunotherapy for glioma patients.
Liu
Gentao
G
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. liug@cshs.org
Yu
John S
JS
Zeng
Gang
G
Yin
Dong
D
Xie
Dong
D
Black
Keith L
KL
Ying
Han
H
D000951:Antigens, Neoplasm; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005909:Glioblastoma / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D015788:HLA-A1 Antigen / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
C410167:AIM2 protein, human; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015788:HLA-A1 Antigen; D009687:Nuclear Proteins; D010455:Peptides; D012333:RNA, Messenger; D012313:RNA; D007371:Interferon-gamma