AIM-2: A Novel Tumor Antigen is Expressed and Presented by... : Journal of Immunotherapy (original) (raw)

Basic Studies

Liu, Gentao*; Yu, John S.*; Zeng, Gang†; Yin, Dong‡; Xie, Dong‡ §; Black, Keith L.*; Ying, Han* ||

From the *Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA; †Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA; ‡Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA; §Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China; ||Oncology Division, Berlex Biosciences Inc, Richmond, CA.

Received for publication December 10, 2003; accepted February 27, 2004.

Reprints: Gentao Liu, Room 2094B, Davis Building, 110 George Burns Road, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (e-mail: [email protected]).

Abstract

A ntigen isolated from I mmunoselected M elanoma-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-γ 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.