Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four glioma cell lines not expressing human leukocyte antigen (HLA)-DR or DQ did so after transfection with genes encoding HLA-DR and DQ. The glioma cells had enhanced ability to stimulate allogeneic and autologous responding lymphocytes in the mixed lymphocyte response (MLR). Glioma cells expressing only HLA-DR had weaker MLR enhancement than those expressing both HLA-DR and DQ or only HLA-DQ. Stimulation by transformed glioma cells increased the killing activity of responding lymphocytes against autologous glioma cells 2.0 times. Both HLA-DR and DQ are important in MLR, and the immunogenicity of glioma cells might be increased by transfection with genes encoding these antigens.
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PMID:Expression of MHC class II antigens on human glioma cells modulated by transfection with genes encoding these antigens. 172 9

A subpopulation of tumor-infiltrating lymphocytes (TILs) and the expression of major histocompatibility complex (MHC) antigens of the tumor cells were examined in 14 glioma and 13 metastatic brain tumor tissues. In both tumors, most of the TILs were T lymphocytes, and both phenotypes of the cytotoxic/suppressor and helper/inducer T lymphocyte were found. On examination of MHC antigens, beta 2-microglobulin was shown intensely on tumor cells in all cases, and the monomorphic determinant of the human leukocyte antigen (HLA-DR) was shown in 10 glioma and in 5 metastatic cases. The correlation between the number of TILs and MHC antigen expression on tumor cells was equivocal as a whole in cases of both glioma and metastatic brain tumor.
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PMID:Immunohistochemical analysis of tumor-infiltrating lymphocytes and major histocompatibility antigens in human gliomas and metastatic brain tumors. 325 30

The identification and propagation of T cells with anti-tumor reactivity is critical for understanding the human immune response to tumors, which may possibly be useful in the successful implementation of adoptive immunotherapy against cancer. In order to address this question, we examined the diversity of mRNA transcripts of T-cell receptor (TCR) V alpha and V beta genes in tumor-infiltrating lymphocytes (TIL) of 12 glioma specimens obtained at surgery. Using the polymerase chain reaction (PCR) method and primers for 18 different human TCR V alpha and 22 V beta families to analyze TCR V-(D)-J-C gene rearrangements, we detected a limited expression of TCR variable region, V alpha genes and predominant usage of V alpha 7 within glioma TIL. TCR V beta gene usage was more diverse than that for V alpha, but TCR V beta 13.1 was dominantly expressed in 9 out of 12 patients. In addition, we analyzed the percentage of each V alpha- and V beta-bearing T-cell subpopulation in TIL as well as in peripheral blood lymphocytes (PBL) quantitatively. The distribution of T-cell subpopulation bearing each V alpha or V beta subfamily was variable and uneven in all cases. In 3 cases, the distribution of V alpha 7-bearing T cells in TIL was far higher than in PBL. This phenomenon was not found in T cells bearing TCR V beta 13.1. We also performed human leukocyte antigen (HLA) typing in these patients, and A24(9) was observed in 8 out of 11 patients. Among them all 3 patients who showed a skewed distribution of V alpha 7-bearing T cells in TIL expressed HLA-A24(9). There was no correlation between particular class I or II type and TCR V beta gene usage. From these results, it was strongly suggested that T cells bearing TCR V alpha 7 might be targeted to antigenic determinants on glioma cells, and such T-cell population may be useful as effector cells for cancer immunotherapy.
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PMID:Skewed distribution of TCR V alpha 7-bearing T cells within tumor-infiltrating lymphocytes of HLA-A24(9)-positive patients with malignant glioma. 814 91

EphA2 is a receptor tyrosine kinase and is frequently overexpressed in a wide array of advanced cancers. We demonstrate in the current study that the EphA2 protein is restrictedly expressed in primary glioblastoma multiforme and anaplastic astrocytoma tissues in comparison to normal brain tissues. To evaluate the possibility of targeting EphA2 in glioma vaccine strategies, we stimulated human leukocyte antigen (HLA) A2+ peripheral blood mononuclear cells (PBMCs) obtained from healthy donors and glioma patients with autologous dendritic cells (DCs) loaded with synthetic EphA2883-891 peptide (TLADFDPRV), which has previously been reported to induce interferon-gamma in HLA-A2+ PBMCs. Stimulated PBMCs demonstrated antigen-specific cytotoxic T lymphocyte (CTL) responses as detected by specific lysis of T2 cells loaded with the EphA2883 peptide as well as HLA-A2+ glioma cells, SNB19 and U251, that express EphA2. Furthermore, in vivo immunization of HLA-A2 transgenic HHD mice with the EphA2883-891 peptide resulted in the development of an epitope-specific CTL response in splenocytes, despite the fact that EphA2883-891 is an autoantigen in these mice. Taken together, these data suggest that EphA2883-891 may be an attractive antigen epitope for molecularly targeted glioma vaccines.
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PMID:EphA2 as a glioma-associated antigen: a novel target for glioma vaccines. 1620 73

A CD8+ cytotoxic T lymphocyte (CTL) line was derived from the peripheral blood mononuclear cells of a patient with primary melanoma. The CD8+ CTL line specifically lysed the autologous primary melanoma cells and not the natural killer cell-sensitive K562 cells or lymphokine activated killer cell-sensitive DAUDI cells. When a large panel of human leukocyte antigen (HLA)-matched and -unmatched allogeneic melanoma, glioma, breast and colorectal carcinoma cells was tested as targets in cytolysis assays, 4 HLA-matched and two HLA-unmatched allogeneic metastatic melanoma lines were lysed by the CD8+ CTL. Lysis of autologous and allogeneic melanoma cells was dependent on the effector-to-target cell ratio. Lysis of autologous melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL was HLA-unrestricted. CTL lysis of autologous melanoma cells was CD3 (T cell receptor) dependent and FAS-FAS-L, and CD1 independent. Identification of the melanoma-associated antigen recognized by the HLA-unrestricted CTL may provide a vaccine for a broad population of melanoma patients.
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PMID:CD8+, HLA-unrestricted, cytotoxic T-lymphocyte line against malignant melanoma. 1628 81

The development of T cell-based immunotherapies of cancer depends on the identification of tumor-associated antigens capable of eliciting tumor-directed cytotoxic T cell responses. In malignant glioma the number of well-defined target antigens for cytotoxic T lymphocytes (CTLs) is still very limited. Recently, we demonstrated the abundant and specific overexpression of the transcription factor SOX11 in malignant glioma. Here, we describe the SOX11-derived peptide LLRRYNVAKV which is capable of inducing human leukocyte antigen-A*0201-restricted and tumor-reactive CTLs. This novel CTL epitope may serve as an attractive candidate for a T cell-based immunotherapy of glioma.
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PMID:Identification of a naturally processed T cell epitope derived from the glioma-associated protein SOX11. 1650 79

Restricted and high-level expression of interleukin-13 receptor alpha2 (IL-13Ralpha2) in a majority of human malignant gliomas makes this protein an attractive vaccine target. We have previously described the identification of the IL-13Ralpha2(345-353) peptide as a human leukocyte antigen-A2 (HLA-A2)-restricted CTL epitope. However, as it remains unclear how efficiently peptide-based vaccines can induce specific CTLs in patients with malignant gliomas, we have examined whether analogue epitopes could elicit heteroclitic antitumor T-cell responses versus wild-type peptides. We have created three IL-13Ralpha2 analogue peptides by substitutions of the COOH-terminal isoleucine (I) for valine (V) and the NH(2)-terminal tryptophan (W) for either alanine (A), glutamic acid (E), or nonsubstituted (W; designated as 1A9V, 1E9V, and 9V, respectively). In comparison with the native IL-13Ralpha2 epitope, the analogue peptides 9V and 1A9V displayed higher levels of binding affinity and stability in HLA-A2 complexes and yielded an improved stimulatory index for patient-derived, specific CTLs against the native epitope expressed by HLA-A2(+) glioma cells. In HLA-A2-transgenic HHD mice, immunization with the peptides 9V and 1A9V induced enhanced levels of CTL reactivity and protective immunity against an intracranial challenge with IL13Ralpha2-expressing syngeneic tumors when compared with vaccines containing the native IL-13Ralpha2 epitope. These findings indicate highly immunogenic IL-13Ralpha2 peptide analogues may be useful for the development of vaccines capable of effectively expanding IL-13Ralpha2-specific, tumor-reactive CTLs in glioma patients.
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PMID:Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responses. 1674 Jul 28

One promising modality in the treatment of malignant glioma is specific immunotherapy. However, this modality requires information about target antigens and their epitope peptides that are recognized by T cells. In this study, we searched for new target candidates in specific immunotherapy for malignant glioma by utilizing cDNA microarray technology to compare gene expressions in malignant glioma tissues to those in benign glioma and a panel of normal tissues. The selected genes included three members of the kinesin superfamily proteins (KIFs): KIF1C, KIF3C, and KIF21B. RT-PCR showed that these three genes were expressed in the majority of glioma cell lines. These antigen-derived 25 peptides, which had the ability to bind to human leukocyte antigen (HLA)-A24 molecules, were first screened for their ability to be recognized by the immunoglobulin G of glioma patients, and then tested for their potential to induce peptide-specific and glioma-reactive cytotoxic T lymphocytes (CTLs) from the peripheral blood mononuclear cells of HLA-A24+ glioma patients. The results showed that the KIF1C149-158 and KIF3C512-520 peptides efficiently induced HLA-A24-restricted and glioma-reactive CD8+ T cells. These results suggest the existence of KIF-reactive CTL precursors in glioma patients, and should facilitate the development of specific immunotherapies for malignant glioma.
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PMID:Kinesin superfamily protein-derived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in human leukocyte antigen-A24+ glioma patients. 1727 44

Two immunoresistant (IR) glioma cell variants, 13-06-IR29 and 13-06-IR30, were cloned from 13-06-MG glioma cell populations after receiving continuous immunoselective pressure from multiple alloreactive cytotoxic T lymphocyte (aCTL) preparations. Reapplication of aCTL immunoselective pressure to the IR clones, displaying a partial regain in sensitivity to aCTL after removal of the selective pressure, restored the resistance. The IR variants exhibited cross-resistance to non-human leukocyte antigen (HLA)-restricted effector cells and gamma-irradiation, but not to carmustine. The IR clones were characterized for factors that might contribute to the immunoresistance. The aCTL adhesion to extracellular matrix extracts derived from either the IR clones or the parental cells was similar and not impaired. Furthermore, aCTL binding to parental cells and IR clones was equal. Down-regulation of the cell recognition molecules, class I HLA or intercellular adhesion molecule-1 (ICAM-1), that would inhibit their recognition by aCTL was not observed on the IR clones. The down-regulation of Fas by the IR clones correlated with their resistance to FasL-induced apoptosis. HLA-G or FasL that might provide an immunotolerant environment or provide a means of counterattack to aCTL, respectively, were not associated with the IR phenotype. The aCTL, coincubated with the IR clones and parental cells, displayed up-regulation of multiple secreted cytokines. A significant up-regulation of bioactive transforming growth factor (TGF)-beta was observed in the IR clones compared with the parental cells. These data suggest that increased secretion of bioactive TGF-beta may inhibit aCTL lysis of the IR clones. Disruption of the TGF-beta signaling pathway may circumvent the resistance.
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PMID:Cellular and functional characterization of immunoresistant human glioma cell clones selected with alloreactive cytotoxic T lymphocytes reveals their up-regulated synthesis of biologically active TGF-beta. 1741 17

Interleukin-13 receptor alpha2 (IL-13Ralpha2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. The present study is a report of a novel approach of targeting malignant glioma with IL-13Ralpha2-specific cytotoxic T lymphocyte (CTL) induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with human leukocyte antigen (HLA)-A2-restricted IL-13Ralpha2(345-353) peptide-pulsed T2 cells. The induced CTL showed specific lysis against T2 cells pulsed with the peptide and HLA-A2+ glioma cells expressing IL-13R2(345-353), while HLA-A2 glioma cell lines that express IL-13Ralpha2(345-353) could not be recognized by CTL. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. These results suggest that the induced CTL specific for IL-13Ralpha2(345-353) peptide could be a potential target of specific immunotherapy for HLA-A2 patients with malignant glioma.
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PMID:Induction of cytotoxic T lymphocytes specific to malignant glioma using T2 cells pulsed with HLA-A2-restricted interleukin-13 receptor alpha 2 peptide in vitro. 1780 58


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