PMID- 17255279 OWN - NLM STAT- MEDLINE DCOM- 20070424 LR - 20210102 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 13 IP - 2 Pt 1 DP - 2007 Jan 15 TI - Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. PG - 566-575 LID - 10.1158/1078-0432.CCR-06-1576 [doi] AB - 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, 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. FAU - Zhang, Jian Gang AU - Zhang JG AD - Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California. AD - Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California. FAU - Eguchi, Junichi AU - Eguchi J AD - Neurological Surgery, University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania. FAU - Kruse, Carol A AU - Kruse CA AD - La Jolla Institute for Molecular Medicine, San Diego, California. FAU - Gomez, German G AU - Gomez GG AD - La Jolla Institute for Molecular Medicine, San Diego, California. FAU - Fakhrai, Habib AU - Fakhrai H AD - NovaRx Corporation, San Diego, California. FAU - Schroter, Stephanie AU - Schroter S AD - University of California, San Diego Cancer Center, La Jolla, California. FAU - Ma, Wenxue AU - Ma W AD - University of California, San Diego Cancer Center, La Jolla, California. FAU - Hoa, Neil AU - Hoa N AD - Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California. AD - Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California. FAU - Minev, Boris AU - Minev B AD - University of California, San Diego Cancer Center, La Jolla, California. FAU - Delgado, Christina AU - Delgado C AD - Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California. AD - Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California. FAU - Wepsic, H Terry AU - Wepsic HT AD - Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California. AD - Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California. FAU - Okada, Hideho AU - Okada H AD - Neurological Surgery, University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania. FAU - Jadus, Martin R AU - Jadus MR AD - Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California. AD - Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California. LA - eng GR - P01 NS 40923/NS/NINDS NIH HHS/United States GR - F31 CA 94834/CA/NCI NIH HHS/United States GR - R44 CA 105964/CA/NCI NIH HHS/United States GR - F31 CA094834/CA/NCI NIH HHS/United States GR - NS 046463/NS/NINDS NIH HHS/United States GR - R44 CA105964/CA/NCI NIH HHS/United States GR - P01 NS040923/NS/NINDS NIH HHS/United States GR - NS 056300/NS/NINDS NIH HHS/United States GR - R21 NS056300/NS/NINDS NIH HHS/United States GR - R21 NS046463/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antigens) RN - 0 (Antineoplastic Agents) RN - 0 (HLA Antigens) SB - IM MH - Antigens/*biosynthesis MH - Antineoplastic Agents/*pharmacology MH - Brain Neoplasms/*immunology/therapy MH - Cell Line, Tumor MH - Dendritic Cells/*cytology MH - Flow Cytometry MH - Genes, MHC Class I MH - Glioma/*immunology/*therapy MH - HLA Antigens/biosynthesis MH - Humans MH - Immunotherapy/instrumentation/*methods MH - Microscopy, Fluorescence MH - Phenotype MH - Transplantation, Homologous PMC - PMC4030524 MID - NIHMS573441 EDAT- 2007/01/27 09:00 MHDA- 2007/04/25 09:00 PMCR- 2014/05/22 CRDT- 2007/01/27 09:00 PHST- 2007/01/27 09:00 [pubmed] PHST- 2007/04/25 09:00 [medline] PHST- 2007/01/27 09:00 [entrez] PHST- 2014/05/22 00:00 [pmc-release] AID - 10.1158/1078-0432.CCR-06-1576 [doi] PST - ppublish SO - Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):566-575. doi: 10.1158/1078-0432.CCR-06-1576.