Glioma-expressed antigen 2 (GLEA2): a novel protein that can elicit immune responses in glioblastoma patients and some controls

Abstract

SUMMARYGlioma constitutes the most frequent brain tumour in man with glioblastoma as the most prevalent and malignant type. The average survival time of less than 16 months underlines the need for improvements in diagnosis and therapy. Here, we report the identification of a novel antigen termed glioma-expressed antigen 2 (GLEA2) causing a frequent immune response in glioma patients. Screening of 450 000 clones from a glioblastoma lambda zap expression library with autologous patient serum revealed a group of five serum-positive clones sharing a high sequence homology. Further sequence analysis showed a sequence homology to a hepatocellular carcinoma associated antigen 58 (HCA58).

Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

“…After analysing 62 sera of glioblastoma patients, we found 15 sera (24.2%) positive for GLEA1 autoantibodies, 30 sera (48.4%) positive for GLEA2 autoantibodies and 35 sera (56.5%) positive for PHF3 autoantibodies. The frequencies of these autoantibodies in patients with glioblastoma are consistent with our previously published study with a smaller number of glioblastoma patients 16,17 (Fig. 1).…”

“…16,17 Detection of antigen-autoantibody complexes by a secondary antibody to the heavy-chain constant region of human IgG was performed as described in Material and Methods. After analysing 62 sera of glioblastoma patients, we found 15 sera (24.2%) positive for GLEA1 autoantibodies, 30 sera (48.4%) positive for GLEA2 autoantibodies and 35 sera (56.5%) positive for PHF3 autoantibodies.…”

“…This view is further supported by our finding that both antigens are putative transcription factors and have PHD-finger or zinc-finger domains, respectively. 16,17 However, further knowledge of the specific cause of the immunogenicity of GLEA2 and PHF3, e.g., point mutations or altered expressions, is required to finally answer the question about the biologic mechanisms that are involved in the antibody response.…”

“…9 SEREX is a powerful method to identify tumor autoantibodies in patient sera as shown for various different tumor types including glioblastoma. [9][10][11][12][13][14][15][16][17] The majority of the SEREXbased studies are aimed toward the identification of novel tumorexpressed antigens that elicit an antibody response in patients bearing the tumors. By contrast, a limited number of antigens identified by SEREX has been further characterized, most notably NY-ESO1.…”

“…11 However, none of these autoantibodies identified by SEREX were correlated with prolonged survival. We previously identified GLEA1, GLEA2 16 and PHF3 17 as glioblastoma-associated immunogenic antigens; all of them encoded by hitherto unknown genes. Herein, we present them to be the first frequently occurring autoantibodies, which are directed against tumor-associated antigens and correlated with prolonged survival of patients with glioblastoma multiforme.…”