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Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics

Authors' Affiliations: ¹ Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California; ² Pathology Department, Neuro-oncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California; ³ Neurological Surgery, University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania; ⁴ La Jolla Institute for Molecular Medicine; ⁵ NovaRx Corporation, San Diego, California; and ⁶ University of California, San Diego Cancer Center, La Jolla, California

Requests for reprints: Martin R. Jadus, Diagnostic and Molecular Medicine Health Care Group, Veterans Affairs Medical Center, Box 113, 5901 East 7th Street, Long Beach, CA 90822. Phone: 562-826-8000, ext. 4079; Fax: 562-826-5623; E-mail: martin.jadus{at}med.va.gov.

Purpose: Allogeneic glioma cell lines that are partially matched to the patient at class I human leukocyte antigen (HLA) loci and that display tumor-associated antigens (TAA) or antigenic precursors [tumor antigen precursor proteins (TAPP)] could be used for generating whole tumor cell vaccines or, alternatively, for extraction of TAA peptides to make autologous dendritic cell vaccines.

Experimental Design: Twenty human glioma cell lines were characterized by molecular phenotyping and by flow cytometry for HLA class I antigen expression. Twelve of the 20 cell lines, as well as analyses of freshly resected glioma tissues, were further characterized for protein and/or mRNA expression of 16 tumor antigen precursor proteins or TAA.

Results: These 20 human glioma cell lines potentially cover 77%, 85%, and 78% of the U.S. Caucasian population at HLA-A, HLA-B, and HLA-C alleles, respectively. All cells exhibited multiple TAA expressions. Most glioma cells expressed antigen isolated from immunoselected melanoma-2 (Aim-2), B-cyclin, EphA2, GP100, ß1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13R2, Her2/neu, hTert, Mage, Mart-1, Sart-1, and survivin. Real-time PCR technology showed that glioblastoma specimens expressed most of the TAA as well. Tumor-infiltrating lymphocytes and CD8⁺ CTL killed T2 cells when loaded with specific HLA-A2⁺ restricted TAA, or gliomas that were both HLA-A2⁺ and also positive for specific TAA (Mart-1, GP100, Her2/neu, and tyrosinase) but not those cells negative for HLA-A2 and/or lacking the specific epitope.

Conclusions: These data provide proof-in-principle for the use of allogeneic, partially HLA patient–matched glioma cells for vaccine generation or for peptide pulsing with allogeneic glioma cell extracts of autologous patient dendritic cells to induce endogenous CTL in brain tumor patients.