Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics.
OBJECTIVE
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.


METHODS
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.
Zhang
Jian Gang
JG
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California.|Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California.
Eguchi
Junichi
J
Neurological Surgery, University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania.
Kruse
Carol A
CA
La Jolla Institute for Molecular Medicine, San Diego, California.
Gomez
German G
GG
La Jolla Institute for Molecular Medicine, San Diego, California.
Fakhrai
Habib
H
NovaRx Corporation, San Diego, California.
Schroter
Stephanie
S
University of California, San Diego Cancer Center, La Jolla, California.
Ma
Wenxue
W
University of California, San Diego Cancer Center, La Jolla, California.
Hoa
Neil
N
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California.|Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California.
Minev
Boris
B
University of California, San Diego Cancer Center, La Jolla, California.
Delgado
Christina
C
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California.|Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California.
Wepsic
H Terry
HT
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California.|Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California.
Okada
Hideho
H
Neurological Surgery, University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania.
Jadus
Martin R
MR
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, California.|Pathology Department, Neurooncology Program, Chao Cancer Center, University of California, Irvine, Irvine, California.
D000941:Antigens / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D005910:Glioma / Q000276:immunology* / Q000628:therapy*; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D007167:Immunotherapy / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence; D010641:Phenotype; D014184:Transplantation, Homologous
D000941:Antigens; D000970:Antineoplastic Agents; D006680:HLA Antigens