Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics.
Abstract | PURPOSE: 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, beta1,6-N-acetylglucosaminyltransferase V (GnT-V), IL13Ralpha2, 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.
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Authors | 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, Martin R Jadus |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 2 Pt 1
Pg. 566-575
(Jan 15 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17255279
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antigens
- Antineoplastic Agents
- HLA Antigens
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Topics |
- Antigens
(biosynthesis)
- Antineoplastic Agents
(pharmacology)
- Brain Neoplasms
(immunology, therapy)
- Cell Line, Tumor
- Dendritic Cells
(cytology)
- Flow Cytometry
- Genes, MHC Class I
- Glioma
(immunology, therapy)
- HLA Antigens
(biosynthesis)
- Humans
- Immunotherapy
(instrumentation, methods)
- Microscopy, Fluorescence
- Phenotype
- Transplantation, Homologous
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