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  • 1
    Electronic Resource
    Electronic Resource
    HLA-Dr-expressing CD8bright cells are only temporarily present in the circulation during subcutaneous recombinant interleukin-2 therapy in renal cell carcinoma patients (1993)
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 198-204 
    Details
    ISSN: 1432-0851
    Keywords: Renal cell carcinoma ; rIL-2 ; Lymphocyte phenotype ; HLA-Dr
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of subcutaneous recombinant interleukin-2 (rIL-2) therapy on the “activation status” of peripheral blood lymphocytes (PBL) of 17 renal cell carcinoma patients was investigated in a longitudinal study. The expression of the activation markers HLA-Dr and CD25 on cytotoxic T cells, helper T cells, and natural killer (NK) cells, was analysed using two-colour flow cytometry of whole-blood samples. In addition, the ability of isolated PBL to proliferate in vitro in response to various stimuli was investigated. The absolute amounts of NK cells and HLA-DR-expressing NK cells increased continuously during the whole course of therapy. The absolute amounts of T cells and HLA-Dr-expressing T cells, however, showed an early increase only during the first 1 or 2 weeks of therapy, after which the absolute amounts of HLA-Dr-expressing T cells decreased. In particular, the absolute amount of HLA-Dr-expressing CD8bright+ T cells was significantly lowered in the second half of therapy. PBL collected on day 7 of therapy (post-cycle-1 PBL) showed, as compared to those collected prior to therapy (pretherapy PBL), a decreased proliferative response in vitro after stimulation with phytohaemagglutinin, concanavalin A, soluble CD3 mAb (WT32) or rIL-2. This decreased in vitro response of post-cycle-1 PBL was also reflected in a decrease in the percentage of CD8bright+ T cells expressing HLA-Dr in cultures with rIL-2 or CD3 mAb, in contrast to cultures of pretherapy PBL, which showed an increase of this percentage. We conclude that T cells are the predominantly stimulated subpopulation during the first 2 weeks of subcutaneous rIL-2 therapy. The significant decrease in the absolute amounts of HLA-Dr-expressing T cells in the peripheral blood during the second half of therapy may partly be explained by a decreased responsiveness to rIL-2, but a selective redistribution of HLA-Dr-expressing cells may also be involved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01741092
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  • 2
    Electronic Resource
    Electronic Resource
    Poor induction of interleukin-2 receptor expression on CD8bright+ cells in whole blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 53-60 
    Details
    ISSN: 1432-0851
    Keywords: Key words: Whole blood assay – IL-2R expression – CD3 stimulation – IFNγ Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To induce better stimulation of T cells during recombinant interleukin-2 (rIL-2) therapy of renal cell carcinoma patients, pretreatment with low-dose CD3 monoclonal antibody (mAb) has been proposed. However, in our clinic, such a treatment did not induce additional activation of T cells. To investigate this we performed whole blood cell cultures with rIL-2 or CD3 mAb as a stimulant. Cultures using isolated blood mononuclear cells were used as a control. When stimulated by the addition of rIL-2, the lymphocyte composition and activation of whole blood cultures did not differ from those of mononuclear cell (MNC) cultures. However, when stimulation was performed with CD3 mAb, CD8bright+ cells in whole blood cultures were not or only minimally induced to express CD25 or IL-2 receptor β (IL-2Rβ). This is in contrast to the situation found in MNC cultures where all CD8bright+ cells expressed CD25 or IL-2Rβ to a high extent at the end of culture. When rIL-2 or recombinant interferon γ (rIFNγ) was added to whole blood cultures together with CD3 mAb, significantly more CD8bright+ cells were induced to express CD25 or IL-2Rβ. These results suggest that whole blood cultures represent the in vivo situation better than MNC cultures. In addition, the results suggest that, also in vivo, administration of low-dose CD3 mAb alone might not be sufficient to induce IL-2R expression on CD8bright+ cells, and would therefore not induce additional specific T cell activation in rIL-2-based immunotherapy. The presented results suggest that in vivo simultaneous administration of rIFNγ or rIL-2 with low-dose CD3 mAb might induce better stimulation of CD8+ T cells than CD3 mAb only.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01517170
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  • 3
    Electronic Resource
    Electronic Resource
    Poor induction of interleukin-2 receptor expression on CD8bright+ cells in whole blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 53-60 
    Details
    ISSN: 1432-0851
    Keywords: Whole blood assay ; IL-2R expression ; CD3 stimulation ; IFNγ Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To induce better stimulation of T cells during recombinant interleukin-2 (rIL-2) therapy of renal cell carcinoma patients, pretreatment with low-dose CD3 monoclonal antibody (mAb) has been proposed. However, in our clinic, such a treatment did not induce additional activation of T cells. To investigate this we performed whole blood cell cultures with rIL-2 or CD3 mAb as a stimulant. Cultures using isolated blood mononuclear cells were used as a control. When stimulated by the addition of rIL-2, the lymphocyte composition and activation of whole blood cultures did not differ from those of mononuclear cell (MNC) cultures. However, when stimulation was performed with CD3 mAb, CD8bright+ cells in whole blood cultures were not or only minimally induced to express CD25 or IL-2 receptor β (IL-2R\). This is in contrast to the situation found in MNC cultures where all CD8bright+ cells expressed CD25 or IL-2Rß to a high extent at the end of culture. When rIL-2 or recombinant interferon γ (rIFNγ) was added to whole blood cultures together with CD3 mAb, significantly more CD8bright+ cells were induced to express CD25 or IL-2Rß. These results suggest that whole blood cultures represent the in vivo situation better than MNC cultures. In addition, the results suggest that, also in vivo, administration of low-dose CD3 mAb alone might not be sufficient to induce IL-2R expression on CD8bright+ cells, and would therefore not induce additional specific T cell activation in rIL-2-based immunotherapy. The presented results suggest that in vivosimultaneous administration of rIFNγ or rIL-2 with low-dose CD3 mAb might induce better stimulation of CD8+ T cells than CD3 mAb only.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01517170
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  • 4
    Electronic Resource
    Electronic Resource
    The immunobiological effects of interleukin-2 in vivo (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 207-216 
    Details
    ISSN: 1432-0851
    Keywords: Immunotherapy ; T cell activation ; Capillary leak syndrome ; Cytokines ; Adhesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525983
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  • 5
    Electronic Resource
    Electronic Resource
    The immunobiological effects of interleukin-2 in vivo (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 207-216 
    Details
    ISSN: 1432-0851
    Keywords: Key words: Immunotherapy – T cell activation – Capillary leak syndrome – Cytokines – Adhesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525983
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  • 6
    Electronic Resource
    Electronic Resource
    An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy (1999)
    Springer
    Cancer immunology immunotherapy 48 (1999), S. 303-311 
    Details
    ISSN: 1432-0851
    Keywords: Key words Transgenic ; Rat ; EGP-2 ; GA733-2 ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or Ep-CAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate treatment-associated effects and side-effects on tumor and normal tissue respectively, we generated an EGP-2-expressing transgenic Wistar rat. To express the cDNA of the EGP-2 in an epithelium-specific manner, the 5′ and 3′ distal flanking regions of the human keratin 18 (K18) gene were used. EGP-2 protein expression was observed in the liver and pancreas, whereas EGP-2 mRNA could also be detected in lung, intestine, stomach and kidney tissues. In this rat, EGP-2-positive tumors can be induced by injecting a rat-derived carcinoma cell line transfected with the GA733-2 cDNA encoding EGP-2. Transgenic rats were used to study specific in vivo localization of an i.v. anti-EGP-2 monoclonal antibody, MOC31, applied i.v. Immunohistochemical analyses showed the specific localization of MOC31 in s.c. induced EGP-2-positive tumors, as well as in the liver. In contrast, in EGP-2-transgenic rats, MOC31 did not bind to EGP-2-negative tumors, the pancreas, or other normal tissues in vivo. In conclusion, an EGP-2-transgenic rat model has been generated that serves as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050579
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  • 7
    Electronic Resource
    Electronic Resource
    Tumor Vascular Endothelium: Barrier or Target in Tumor Directed Drug Delivery and Immunotherapy (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 2-10 
    Details
    ISSN: 1573-904X
    Keywords: tumor vascular endothelium ; targeting ; drug delivery ; immunotherapy ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The therapy of solid tumors with conventional chemotherapeutics, drug delivery preparations and immuno-modulatory agents directed against the tumor cells is corrupted by a major barrier presented by the tumor vasculature. Permeability of the tumor blood vessels for transport of small molecules and macromolecular drug-carrier conjugates is only sufficient in the blood vessels at the tumor-host interface. Downregulation of the expression of adhesion molecules, required for the facilitation of immune cell recruitment, by the tumor vascular endothelium results in an escape of the tumor from host defence. New therapeutic approaches for the treatment of solid tumors are aimed at the tumor vasculature, either at the endothelial cells themselves or at basement membrane or tumor stroma components. Angiogenesis can be directly blocked with angiogenesis inhibitors, while angiogenesis related factors can serve as tumor vasculature specific epitopes for drug delivery strategies. Some glycoproteins expressed by tumor endothelial cells or present in the basement membrane and tumor stroma are also potential tumor selective targets. Therapeutic modalities that are suitable for site specific delivery are agents that increase tumor accumulation of (targeted) chemo/radiotherapeutics through increasing tumor vascular permeability. The observation that for tumor growth the blood supply is a limiting factor, led to the development of strategies to inhibit angiogenesis or block the tumor blood flow. Manipulation of the expression of endothelial cell adhesion molecules by selectively delivering modulatory agents at or in the tumor vascular endothelial cells may induce (bispecific antibody mediated) host defense activity directed against the tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012038930172
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  • 8
    Electronic Resource
    Electronic Resource
    Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer (1987)
    [s.l.] : Nature Publishing Group
    Nature 330 (1987), S. 578-581 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Analysis of five SCLC cell lines revealed the presence of at least one morphologically normal and one deleted homologue of chromosome 3 per cell line. The shortest region of overlap for the deletion originally reported as 3pl4-3p23 (ref. 6), could be narrowed to 3p21 distal-p22 (Fig. 1). A human ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/330578a0
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  • 9
    Electronic Resource
    Electronic Resource
    Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells: intracellular localization of tumor necrosis factor α and interleukin 1β detected with a three-color immunofluorescence technique (1996)
    Springer
    Histochemistry and cell biology 106 (1996), S. 593-598 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Lipopolysaccharide (LPS) can induce monocytes to produce various cytokines such as tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). In the present study, the kinetics of both intracellular and extracellular accumulation of TNFα and IL-1β in LPS stimulated mononuclear cell (MNC) cultures has been determined. A three-color-immunofluorescence technique was used to detect intracellular accumulation of cytokines. Intracellular accumulation of TNFα in monocytes starts shortly after initiation of the culture; i.e., TNFα is detectable after 1 h, reaching a peak level after 3–4 hours with 50–65% of monocytes staining positive. In parallel with its increased intracellular presence, TNFα was also found in the culture supernatant. The intracellular accumulation of IL-1β in monocytes became detectable after 2 h of culture in the presence of LPS. After 4 h, a plateau was reached, with 90% of the monocytes being positive. In parallel, but with a little delay, IL-1β could be detected in the culture supernatnant. TNFα and IL-1β can be produced simultaneously in the same monocytes as was shown by a three-color-immunofluorescence technique. It is concluded that TNFα and IL-1β are good parameters for the early measurement of monocyte activation and that both the intracellular accumulation in monocytes and the amount of secreted cytokines can be used for such a purpose. The intracellular accumulation in monocytes can be measured by the three-color-immuno-fluorescence technique described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02473275
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  • 10
    Electronic Resource
    Electronic Resource
    Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells: intracellular localization of tumor necrosis factor α and interleukin 1β detected with a three-color immunofluorescence technique (1996)
    Springer
    Histochemistry and cell biology 106 (1996), S. 593-598 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Lipopolysaccharide (LPS) can induce monocytes to produce various cytokines such as tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). In the present study, the kinetics of both intracellular and extracellular accumulation of TNFα and IL-1β in LPS stimulated mononuclear cell (MNC) cultures has been determined. A three-color-immunofluorescence technique was used to detect intracellular accumulation of cytokines. Intracellular accumulation of TNFα in monocytes starts shortly after initiation of the culture; i.e., TNFα is detectable after 1 h, reaching a peak level after 3–4 hours with 50–65% of monocytes staining positive. In parallel with its increased intracellular presence, TNFα was also found in the culture supernatant. The intracellular accumulation of IL-1β in monocytes became detectable after 2 h of culture in the presence of LPS. After 4 h, a plateau was reached, with 90% of the monocytes being positive. In parallel, but with a little delay, IL-1β could be detected in the culture supernatant. TNFα and IL-1β can be produced simultaneously in the same monocytes as was shown by a three-color-immunofluorescence technique. It is concluded that TNFα and IL-1β are good parameters for the early measurement of monocyte activation and that both the intracellular accumulation in monocytes and the amount of secreted cytokines can be used for such a purpose. The intracellular accumulation in monocytes can be measured by the three-color-immunofluorescence technique described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004180050081
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    Paper (German National Licenses)
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