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  • 1
    Electronic Resource
    Electronic Resource
    Specific cytotoxic T lymphocytes in gene therapy (1997)
    Springer
    Journal of molecular medicine 75 (1997), S. 259-266 
    Details
    ISSN: 1432-1440
    Keywords: Key words Recombinant T cells receptors ; Retroviral gene transfer vectors ; Primary T cells ; Transforming growth factor β
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cytotoxic T lymphocytes possess the capacity to lyse target cells which express antigens on their surface recognized by the T cell receptor. These cells are crucial in the body’s defense against foreign antigens. It has long been a goal of tumor biology to utilize T cells, specialized in the elimination of unwanted cells, for the treatment of cancer. The killing activity of T lymphocytes is restricted to specific antigen-presenting cells. For this reason the use of cytotoxic T cells in the elimination of cancer cells is limited to cancer cells which present neoantigens on their surface. To circumvent this limitation we describe a procedure in which the ζ component of the T cell receptor is genetically manipulated and equipped with an extracellular recognition domain. Introduction of a chimeric gene, consisting of the ζ chain of the T cell receptor and a single-chain antibody domain, into cytotoxic T lymphocytes results in T cells with a predetermined recognition specificity for particular tumor cells. The MHC restriction of target cell recognition can be avoided and tumor cells recognized by the single chain antibody domain can be recognized and lysed. Retroviral-mediated gene transduction was used to introduce chimeric ζ chain constructs into primary T cells of mice. The cocultivation of retrovirus producing helper cells with in vitro activated T lymphocytes led to a high gene transduction efficiency into primary T cells. These primary T cells assumed a predetermined specificity for target cell recognition and lysis. The production and provision of tumor cell specific T lymphocytes might not be sufficient to eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that transplanted tumors secrete transforming growth factor β and thereby stifle the action of lymphocytes. We suggest that a coordinated strategy including the suppression of tumor cells specific antilymphocyte action and the provision of tumor cell specific T cells might be required to successfully eliminate tumor cells in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050111
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Purification and properties of benzyl alcohol dehydrogenase from a denitrifying Thauera sp. (1995)
    Springer
    Archives of microbiology 163 (1995), S. 418-423 
    Details
    ISSN: 1432-072X
    Keywords: Key wordsThauera ; Toluene ; Benzyl alcohol ; Benzyl alcohol dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Toluene and related aromatic compounds are anaerobically degraded by the denitrifying bacterium Thauera sp. strain K172 via oxidation to benzoyl-CoA. The postulated initial step is methylhydroxylation of toluene to benzyl alcohol, which is either a free or enzyme-bound intermediate. Cells grown with toluene or benzyl alcohol contained benzyl alcohol dehydrogenase, which is possibly the second enzyme in the proposed pathway. The enzyme was purified from benzyl-alcohol-grown cells and characterized. It has many properties in common with benzyl alcohol dehydrogenase from Acinetobacter and Pseudo-monas species. The enzyme was active as a homotetramer of 160 kDa, with subunits of 40 kDa. It was NAD+-specific, had an alkaline pH optimum, and was inhibited by thiol-blocking agents. No evidence for a bound cofactor was obtained. Various benzyl alcohol analogues served as substrates, whereas non-aromatic alcohols were not oxidized. The N-terminal amino acid sequence indicates that the enzyme belongs to the class of long-chain Zn2+-dependent alcohol dehydrogenases, although it appears not to contain a metal ion that can be removed by complexing agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00272130
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Costimulation of T-cell proliferation by a chimeric B7-antibody fusion protein (1997)
    Springer
    Cancer immunology immunotherapy 45 (1997), S. 156-158 
    Details
    ISSN: 1432-0851
    Keywords: Key words B7 ; CD80 ; CD86 ; Single-chain antibody ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  T cells require at least two signals for activation and clonal expansion. The first signal conferring specificity is initiated by interaction of the T cell receptor with peptide-bearing MHC molecules. The second, costimulatory signal can be provided by cell-surface molecules on antigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which interact with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of tumor cells we have constructed a chimeric fusion protein, which consists of the extracellular domain of human B7-2 fused to a single-chain antibody domain (scFv) specific for the ErbB2 protein, a type I growth factor receptor overexpressed in a high percentage of human adenocarcinomas. This B7-2225-scFv(FRP5) molecule, expressed in the yeast Pichia pastoris and purified from culture supernatants, binds to B7 counter-receptors and to ErbB2. B7-2225-scFv(FRP5) localizes specifically to the surface of ErbB2-expressing target cells, thereby providing a costimulatory signal, which results in enhanced proliferation of syngeneic T cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050421
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    Paper (German National Licenses)
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