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  • 1
    Electronic Resource
    Electronic Resource
    B cells inhibit induction of T cell-dependent tumor immunity (1998)
    [s.l.] : Nature Publishing Group
    Nature medicine 4 (1998), S. 627-630 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Cytotoxic T lymphocyte (CTL) mediated tumor immunity against major histocompatibility antigen (MHC) class I-positive but class II-negative tumors often requires help from CD4+ T cells. These CD4 cells are activated by MHC class II-positive cells that present tumor derived antigens1,2. Considering ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0598-627
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  • 2
    Electronic Resource
    Electronic Resource
    Adenovirus-mediated combined suicide gene and interleukin-2 gene therapy for the treatment of established tumor and induction of antitumor immunity (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 683-689 
    Details
    ISSN: 1432-1335
    Keywords: Key words Cytosine deaminase ; Suicide gene ; Gene therapy ; Adenovirus ; Interleukin 2 ; Cytotoxic T lymphocytes ; Antitumor immunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effect of the combined transfer of a suicide gene and a cytokine gene was evaluated in the present study. Adenoviruses expressing Escherichia coli cytosine deaminase (AdCD) and adenoviruses expressing murine interleukin-2 (AdIL-2) were utilized for the treatment of established tumors. The mice were inoculated s.c. with FBL-3 erythroleukemia cells and 3 days later received an intratumoral injection of AdCD in the presence or absence of AdIL-2 followed by intraperitoneal 5-fluorocytosine (5-FC) administration. The results demonstrated that tumor-bearing mice treated with AdCD/5-FC in combination with AdIL-2 showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdCD/5-FC, AdIL-2, adenovirus expressing β-galactosidase/5-FC or phosphate-buffered saline. The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD4+ and CD8+ T cells infiltrating the tumor after combined therapy. The splenic natural killer and cytotoxic T lymphocyte activities increased significantly in the mice after combined therapy with AdCD/5-FC/AdIL-2. Our results demonstrate that therapy combining a suicide gene and IL-2 gene can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050232
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  • 3
    Electronic Resource
    Electronic Resource
    Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 602-608 
    Details
    ISSN: 1432-1335
    Keywords: Key words Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Gene transfection ; Melanoma cells ; Adhesion ; Cytotoxicity ; MHC class I ; ICAM-1 ; Effector cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the molecular and cellular mechanisms involved in the reduced tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL-6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and phenotypic properties of these genetically engineered melanoma cells in the present study. The cytokine-gene-transfected B16 melanoma cells showed stronger adhesion to the lymphokine-activated killer (LAK) cells or cytotoxic T lymphocytes (CTL), and higher sensitivity to cytotoxicity of LAK cells or CTL. Using fluorescence-activated cell sorting analysis, we found that both MHC class I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfection. The increased level of MHC class I and ICAM-1 expression seems to be responsible for the high sensitivity of these gene-transfected B16 cells to LAK or CTL cytotoxicity because anti-(MHC class I) or anti-ICAM-1 mAb could inhibit the adhesion and cytotoxicity increment simultaneously. The CTL induction was partly inhibited by anti-ICAM-1 mAb and was completely blocked by anti-MHC class I mAb. These results suggested that the decreased tumorigenicity of IL-2-, IL-4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the increased sensitivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cytokine gene transfection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050112
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  • 4
    Electronic Resource
    Electronic Resource
    Chemoattractive effect on the effector cells of the supernatants from melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 88-92 
    Details
    ISSN: 1432-1335
    Keywords: Key words Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Gene transfection ; Effector cells ; Melanoma ; Chemotaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract By using the Boyden chamber system, the chemoattractive activity of the supernatants from the B16 melanoma cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene was investigated. We found that supernatants from IL-2- or IL-6-gene-transfected B16 melanoma cells showed chemoattractive activity on natural killer (NK) cells, CD4+ T cells and CD8+ T cells, while the supernatants from IL-4-gene-transfected B16 melanoma cells showed chemotactic activity on macrophages but not on NK cells and T cells. Further, the chemoattractive activity of the supernatants from cytokine-gene-transfected B16 cells might be the direct effects of the cytokine that they have been engineered to secrete. These results indicate that reduced tumorigenicity and increased immunogenicity of cytokine-gene-transfected B16 cells may be attributed to the direct recruitment of immune effector cells by the secreted cytokine, which plays an important role in the induction of the local antitumor immunity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050139
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  • 5
    Electronic Resource
    Electronic Resource
    Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2 (1995)
    Springer
    Journal of cancer research and clinical oncology 121 (1995), S. 721-728 
    Details
    ISSN: 1432-1335
    Keywords: Interleukin-6 ; Gene therapy ; Cancer vaccine ; Interleukin-2 ; Active immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transfer of cytokine genes into tumor cells has proven a valuable approach for cancer treatment. In order to generate a more effective cancer vaccine, we transfected the human interleukin-6 (IL-6) gene into B16 melanoma cells. A B16 cell clone secreting the highest level of IL-6 was obtained by G418-resistant selection, limiting dilution and IL-6 assay. The IL-6-gene-transfected tumor cells exhibited in vitro growth inhibition, reduced tumorigenicity and decreased metastatic competence. After immunization with the inactivated IL-6-gene-transfected vaccine, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After treatment with the vaccine, the tumorbearing mice showed significant growth inhibition of subcutaneous tumor, reduction in pulmonary metastases and extension of survival time. The above therapeutic effect was better when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrated that IL-6-gene-transfected cancer vaccine has a potent antitumor effect via efficient induction of antitumor immunity, and a better therapeutic effect could be achieved when the vaccine is combined with lowdose IL-2 as adjuvant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01213318
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  • 6
    Electronic Resource
    Electronic Resource
    Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus (1996)
    Springer
    Journal of cancer research and clinical oncology 122 (1996), S. 716-722 
    Details
    ISSN: 1432-1335
    Keywords: Recombinant vaccinia virus ; GM-CSF ; Melanoma ; Gene therapy ; Macrophage ; Metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2×105 B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-geneencoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01209118
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  • 7
    Electronic Resource
    Electronic Resource
    Treatment of human hepatocellular carcinoma by fibroblast-mediated human interferon α gene therapy in combination with adoptive chemoimmunotherapy (1995)
    Springer
    Journal of cancer research and clinical oncology 121 (1995), S. 457-462 
    Details
    ISSN: 1432-1335
    Keywords: Interferon ; Gene therapy ; Fibroblast ; Hepatocellular carcinoma ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The therapeutic effect of the fibroblast-mediated human interferon (IFNα) gene therapy in combination with interleukin-2 (IL-2) activated killer cells (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) on nude mice bearing the human hepatocellular carcinoma (HCC) was investigated. A fibroblast cell clone (NIH3T3-IFNα+) secreting 1024 U/ml human IFNα was obtained from 14 positive clones by BMGNeo-INFα DNA transfection, G418-resistant selection, limiting dilution and assay of IFNα activity. After i.p. implantation of NIH3T3-IFNα+ encapsulated into collagen, serum human IFNα activity could be detected from 12 h to day 15 with a peak at 72 h. AK were prepared from human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated human SMMC 7721 HCC cells. When the NIH3T3-IFNα+ cells were i.p. implanted into the HCC-bearing nude mice, the grown of HCC was inhibited and the survival time of the mice was extended. The growth of HCC was inhibited more obviously when AK was i.v. injected and IL-2 was i.p. injected after the NIH3T3-IFNα+ cells had been implanted. The best therapeutic effect was achieved when NIH3T3-IFNα+ cells were used in combination with IL-2/AK/doxorubicin. All these results suggested that the fibroblast-mediated human IFNα gene therapy could be used to treat the human hepatocellular carcinoma effectively and that when used in combination with IL-2-based adoptive chemoimmunotherapy, the therapeutic effect would be better.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01218361
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