AIM-2: a novel tumor antigen is expressed and presented by human glioma cells

J Immunother. May-Jun 2004;27(3):220-6. doi: 10.1097/00002371-200405000-00006.

Abstract

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.

MeSH terms

  • Antigens, Neoplasm*
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Glioblastoma / metabolism*
  • Glioma / metabolism*
  • HLA-A1 Antigen / chemistry
  • Humans
  • Immunotherapy / methods
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / chemistry
  • Peptides / chemistry
  • RNA / chemistry
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / metabolism
  • Time Factors
  • Up-Regulation

Substances

  • AIM2 protein, human
  • Antigens, Neoplasm
  • DNA, Complementary
  • DNA-Binding Proteins
  • HLA-A1 Antigen
  • Nuclear Proteins
  • Peptides
  • RNA, Messenger
  • RNA
  • Interferon-gamma