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Clinical Cancer Research

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Cancer Therapy: Clinical

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

Jian Gang Zhang, Junichi Eguchi, Carol A. Kruse, German G. Gomez, Habib Fakhrai, Stephanie Schroter, Wenxue Ma, Neil Hoa, Boris Minev, Christina Delgado, H. Terry Wepsic, Hideho Okada and Martin R. Jadus
Jian Gang Zhang
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Junichi Eguchi
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Carol A. Kruse
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German G. Gomez
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Habib Fakhrai
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Stephanie Schroter
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Wenxue Ma
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Neil Hoa
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Boris Minev
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Christina Delgado
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H. Terry Wepsic
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Hideho Okada
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Martin R. Jadus
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DOI: 10.1158/1078-0432.CCR-06-1576 Published January 2007
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Abstract

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, β1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13Rα2, 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.

  • glioma
  • HLA
  • CTLs
  • tumor antigens
  • real time PCR
  • intracellular flow cytometry

Footnotes

  • Grant support: Veterans Affairs Medical Center (M.R. Jadus and H.T. Wepsic), the Avon Breast Cancer Foundation via the University of California at Irvine Cancer Research Program (M.R. Jadus), NIH/National Institute of Neurological Disorders and Stroke grant P01 NS40923 (H. Okada), Clinical Scientist Development Award from Doris Duke Charitable Foundation (H. Okada), 21st Century Scientist Award from James S. McDonnell Foundation (H. Okada), the Copeland Fund of the Pittsburgh Foundation (J. Eguchi and H. Okada), a grant from the Brain Tumor Society (B. Minev), NIH/National Cancer Institute grant R44-CA105964 (H. Fakhrai), NIH grant F31 CA94834 (G.G. Gomez), NIH/National Institute of Neurological Disorders and Stroke grants NS046463 and NS056300 (C.A. Kruse), the R. Herbert and Alma S. Manweiler Memorial Research Fund (C.A. Kruse), and the La Jolla Foundation for Molecular Medicine Research (C.A. Kruse).

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Note: J.G. Zhang and J. Eguchi contributed equally to this work.

    • Accepted November 2, 2006.
    • Received June 30, 2006.
    • Revision received October 6, 2006.
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Clinical Cancer Research: 13 (2)
January 2007
Volume 13, Issue 2
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Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics
Jian Gang Zhang, Junichi Eguchi, Carol A. Kruse, German G. Gomez, Habib Fakhrai, Stephanie Schroter, Wenxue Ma, Neil Hoa, Boris Minev, Christina Delgado, H. Terry Wepsic, Hideho Okada and Martin R. Jadus
Clin Cancer Res January 15 2007 (13) (2) 566-575; DOI: 10.1158/1078-0432.CCR-06-1576

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Antigenic Profiling of Glioma Cells to Generate Allogeneic Vaccines or Dendritic Cell–Based Therapeutics
Jian Gang Zhang, Junichi Eguchi, Carol A. Kruse, German G. Gomez, Habib Fakhrai, Stephanie Schroter, Wenxue Ma, Neil Hoa, Boris Minev, Christina Delgado, H. Terry Wepsic, Hideho Okada and Martin R. Jadus
Clin Cancer Res January 15 2007 (13) (2) 566-575; DOI: 10.1158/1078-0432.CCR-06-1576
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