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  • 1
    Keywords: CANCER ; CELLS ; IN-VITRO ; proliferation ; tumor ; TUMOR-CELLS ; CELL-PROLIFERATION ; Germany ; human ; DISEASE ; ADHESION MOLECULES ; MOLECULES ; RELEASE ; PATIENT ; ACTIVATION ; RESPONSES ; ANTIGEN ; T-CELL ; T-CELLS ; MOLECULE ; cytokines ; IMMUNE-RESPONSES ; antibodies ; antibody ; virus ; UP-REGULATION ; MONOCLONAL-ANTIBODIES ; VACCINE ; SAFETY ; IMMUNE-RESPONSE ; INTERFERON ; INTERFERON-ALPHA ; NEWCASTLE-DISEASE VIRUS ; CANCER PATIENTS ; chemokine ; EFFECTOR ; IMMUNOLOGICAL SYNAPSE ; bispecific antibody ; CYTOTOXICITY ; tumor vaccine ; RE ; NEWCASTLE-DISEASE-VIRUS ; SINGLE-CHAIN ANTIBODY ; bispecific ; Newcastle disease virus ; CD28 COSTIMULATION ; bispecific single chain antibody ; CD3 and CD28 cross-linking
    Abstract: The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety. (c) 2004 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15752830
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  • 2
    Keywords: RECEPTOR ; CANCER ; CELLS ; IN-VITRO ; tumor ; carcinoma ; CELL ; COMBINATION ; Germany ; human ; IN-VIVO ; VITRO ; DISEASE ; PROTEIN ; PROTEINS ; MOLECULES ; MICE ; GENE-TRANSFER ; PATIENT ; ACTIVATION ; INFECTION ; INDUCTION ; ANTIGEN ; T cell ; T cells ; T-CELL ; T-CELLS ; MOLECULE ; BREAST ; virus ; ASSAY ; IMMUNODEFICIENT MICE ; FUSION ; EFFICIENT ; FUSION PROTEINS ; VACCINE ; ELISPOT ; IMMUNOTHERAPY ; FUSION PROTEIN ; AGENT ; ONCOLOGY ; REGRESSION ; RE ; COSTIMULATION ; T-CELL-ACTIVATION ; NEWCASTLE-DISEASE-VIRUS ; Newcastle disease virus ; CD28 COSTIMULATION ; ANTITUMOR VACCINATION ; SHORT-TERM ; viral ; cancer vaccination ; immunocytokine ; IMMUNOGENE THERAPY
    Abstract: T cell costimulation has great therapeutic potential if it can be optimized and controlled. To achieve this, we engineered T cell-activating fusion proteins and immunocytokines that specifically attach to viral antigens of a virus-infected tumor vaccine. We employed the avian Newcastle Disease Virus because this agent is highly efficient for human tumor cell infection, and leads to introduction of viral hemagglutinin-neuraminidase (HN) molecules at the tumor cell surface. Here, we demonstrated the strong potentiation of the T cell stimulatory activity of such a vaccine upon attachment of bispecific or trispecific fusion proteins which bind with one arm to viral HN molecules of the vaccine, and with the other arm either to CD3 (signal 1), to CD28 (costimulatory signal 2a), or to interleukin-2 receptor (costimulatory signal 2b) on T cells. A vaccine with a combination of all three signals triggered the strongest activation of naive human T cells, thereby inducing the most durable bystander antitumor activity in vitro. Adoptive transfer of such polyclonally activated cells into immunodeficient mice bearing human breast carcinoma caused tumor regression. Furthermore, tumor-reactive memory T cells from draining lymph nodes of carcinoma patients could be efficiently reactivated in a short-term ELISpot assay using an autologous tumor vaccine with optimized signals 1 and 2, but not with a similarly modified vaccine from an unrelated tumor cell line. Our data describe new bioactive molecules which in combination with an established virus-modified tumor vaccine greatly augments the antitumor activity of T cells from healthy donors and cancer patients
    Type of Publication: Journal article published
    PubMed ID: 18360705
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  • 3
    Keywords: CANCER ; CELLS ; tumor ; TUMOR-CELLS ; BLOOD ; carcinoma ; CELL ; COMBINATION ; Germany ; human ; DISEASE ; MOLECULES ; PATIENT ; ACTIVATION ; INFECTION ; MECHANISM ; INDUCTION ; CD8(+) T-CELLS ; mechanisms ; T cell ; T cell activation ; T cells ; T-CELL ; T-CELLS ; BINDING ; MOLECULE ; ANTITUMOR-ACTIVITY ; BREAST ; RECOGNITION ; antibodies ; antibody ; TARGET ; virus ; CARCINOMA CELLS ; LYMPHOCYTES ; CARCINOMA-CELLS ; BREAST-CARCINOMA ; VACCINE ; CANCER-PATIENTS ; INTERFERON ; NEWCASTLE-DISEASE VIRUS ; CANCER PATIENTS ; TUMOR CELLS ; EFFECTOR ; HUMAN BREAST ; bispecific antibody ; T-cell response ; tumor vaccine ; APOPTOSIS-INDUCING LIGAND ; MONONUCLEAR-CELLS ; ONCOLOGY ; RE ; COSTIMULATION ; NEWCASTLE-DISEASE-VIRUS ; carcinoma cell ; TUMOR-CELL ; bispecific ; Newcastle disease virus ; VIROTHERAPY ; breast carcinoma ; CD3 and CD28 cross-linking ; ANTITUMOR ; ANTITUMOR ACTIVITIES ; bispecific single-chain antibodies ; CONTACT ; tumor neutralization assay
    Abstract: We recently reported on newly designed virus-targeted bispecific CD3- and CD28-binding molecules for human T-cell activation. When bound via one arm to a human virus-modified tumor cell vaccine, these reagents caused a polyclonal T-cell response and overcame the potential various T-cell evasion mechanisms of tumor cells. In our current study, we demonstrated the induction of strong antitumor activity in human lymphocytes upon coincubation with a virus-modified tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies. Blood mononuclear cells or purified T cells that were coincubated with such a tumor vaccine for 3 days were able to destroy monolayers of human breast carcinoma and other carcinoma cells. Serial transfer to new tumor cell monolayers revealed antitumor cytotoxic activity in such effector cells that lasted for about 10 days. Nontumor target cells appeared to be much less sensitive to the activated effector cells. Although the bispecific molecules alone did not activate effector cells, their binding to virus-infected tumor cells was important and. more effective than their binding to free virus. Antitumor activity of the activated effector cells was mediated through soluble factors as well as through direct cell contact of effector cells with the nontargeted bystander tumor cells. Since the virus-modified tumor vaccine is well tolerated and already exhibits a certain effectiveness in cancer patients, the combination with new bispecific molecules has the potential to introduce additional antitumor effects. The reagents can also be combined with Newcastle Disease Virus (NDV)-based oncolytic virotherapy. (c) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16108015
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  • 4
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 620 (1994), S. 781-785 
    ISSN: 0044-2313
    Keywords: Oxothallate(III) ; Preparation ; Structure ; MAPLE ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Oxidation of Intermetallic Phases: K4{Na2[Tl2O6]} from NaTl and K2O2The hitherto unknown K4{Na2[Tl2O6]} was prepared in form of transparent, yellow single crystals from NaTl and KO1,08 (molar ratio 1:1.3; sealed Ag-cylinder; 450°C, 30 d). The structure determination (four-circle diffractometer, MoKα, 1 280 out of 1 523 Io(hkl), R = 5.75%, Rw = 4.58%) confirms the space group P21/c with a = 641.3 pm, b = 691.1 pm, c = 1188.5 pm, β = 95.69° and Z = 2. As characteristic building units of the structure there are doubles of tetrahedra of [Tl2O6] and [Na2O6]. The compound is isotypic with Cs6[In2O6] and Rb6[Tl2O6]. The Madelung Part of Lattice Energy, MAPLE, the Mean Fictive Ionic Radii, MEFIR, Effective Coordination Numbers, ECoN, and Charge Distribution, CHARDI, are calculated.
    Notes: Bisher unbekanntes K4{Na2[Tl2O6]} wurde durch Oxydation von NaTl mit KO1,08 (1:1,3; geschlossener Ag-Zylinder; 450°C; 30 Tage) in Form transparenter, gelber Einkristalle dargestellt. Die Strukturaufklärung (Vierkreisdiffraktometerdaten, MoKα, 1 280 von 1 523 Io(hkl), R = 5,75%, Rw = 4,58%) erfolgte in der Raumgruppe P21/c mit a = 641,3 pm, b = 691,1 pm, c = 1 188,5 pm, β = 95,69° und Z = 2. Charakteristisches Motiv sind über Kanten verknüpfte, von ihresgleichen „isolierte“ Tetraederdoppel [Tl2O6] und [Na2O6]. Die Verbindung ist isotyp zu Cs6[In2O6] und Rb6[Tl2O6]. Der Madelunganteil der Gitterenergie, MAPLE, die Mittleren fiktiven Ionenradien, MEFIR, Effektive Koordinationszahlen, ECoN, sowie die Ladungsverteilung, CHARDI, werden berechnet.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0044-2313
    Keywords: New basic Oxoindate(III): Na26O3[InO4]4 ; Structure ; MAPLE ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: The First Basic Oxoindate: Na26O3[InO4]4For the first time Na26O3[InO4]4 was obtained by annealing intimate mixtures of Na2O, CdO and elemental In (molar ratio 3.5:1.0:2.0) in closed Ni-cylinders (30 days, 600°C) in form of yellow single crystals. The structure determination by four circle diffractometer data (MoKα, 921 out of 921 Io(hkl), R = 2.53, Rw = 2.18%) confirms the space group 143d (cubic) with a = 1 427.37 pm and Z = 4. All kation are surrounded by tetrahedron of O2-. In3+ is coordinated with O(1) and O(2) (without O(3)) only. There are „isolated“ [InO4]-tetrahedra. The Madelung Part of Lattice Energy, MAPLE, the Mean Fictive Ionic Radii, MEFIR, Effective Coordination Numbers, ECoN, and Charge Distribution, CHARDI, are calculated.
    Notes: Beim Tempern inniger Gemenge von Na2O, CdO und elementarem In (3,5:1,0:2,0) in verschlossenen Ni-Zylindern (30 Tage, 600°C) erhielten wir gelbe Einkristalle von Na26O3[InO4]4. Die Strukturaufklärung (Vierkreisdiffraktometerdaten, MoKα, 921 von 921 Io(hkl), R = 2,53, Rw = 2,18%) erfolgte in der Raumgruppe 143d (kubisch) mit a = 1 427,37 pm und Z = 4. Alle Kationen sind tetraedrisch von O2- umgeben; In3+ jedoch nur von O(1) und O(2) und nicht von O(3). Strukturcharakteristisch sind die „Inseln“ [InO4], auffallend die C.N. 8 für O(3). Der Madelunganteil der Gitterenergie, MAPLE, die Mittleren Fiktiven Ionenradien, MEFIR, Effektive Koordinationszahlen, ECoN, sowie die Ladungsverteilung, CHARDI, werden berechnet.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 620 (1994), S. 777-780 
    ISSN: 0044-2313
    Keywords: New Oxothallate(III) ; Structure ; MAPLE ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: The First Oxothallate(III) with the Formula Type AA4′[MO4]: CsK4[TlO4]For the first time CsK4[TlO4] was obtained by heating intimate mixtures of K2O, CdO and CsTl (molar ratio 3.1:1.0:1.0) in closed Ag-cylinders (25 days, 450°C) in form of yellow, transparent single crystals. The structure determination by four circle diffractometer data (MoKα, 1922 out of 2 094 Io(hkl), R = 2.98, Rw = 2.49) confirms the space group Pbca with lattice constants a = 1 192.1 pm; b = 685.7 pm; c = 2 143.5 pm; Z = 8. The structure is isotypic with Na5[GaO4]. The Madelung Part of Lattice Energy, MAPLE, the Mean Fictive Ionic Radii, MEFIR, Effective Coordination Numbers, ECoN, and Charge Distribution, CHARDI, are calculated.
    Notes: Beim Tempern inniger Gemenge von K2O, CdO und CsTl (3,1:1,0:1,0) in verschlossenen Ag-Zylindern (25 Tage, 450°C) erhielten wir gelbe, transparente Einkristalle von bisher unbekanntem CsK4[TlO4]. Die Strukturaufklärung (Vierkreisdiffraktometerdaten, MoKα, 1922 von 2094 Io(hkl), R = 2,98%, Rw = 2,49%) erfolgte in der Raumgruppe Pbca mit den Gitterkonstanten: a = 1 192,1 pm; b = 685,7 pm; c = 2 143,5 pm; Z = 8. Es liegt Isotypie zu Na5[GaO4] vor. Der Madelunganteil der Gitterenergie, MAPLE, die Mittleren Fiktiven Ionenradien, MEFIR, Effektive Koordinationszahlen, ECoN, sowie die Ladungsverteilung, CHARDI, werden berechnet.
    Additional Material: 5 Tab.
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  • 7
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 619 (1993), S. 1818-1826 
    ISSN: 0044-2313
    Keywords: New Oxoindate(III) ; Structure ; MAPLE Calculations ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: The First Oligooxoindate(III): K14[In4O13]For the first time K14[In4O13] was obtained by heating intimate mixtures of K2O, CdO and elementar In (molar ratio 3.1:1.0:1.0) in closed Ag-cylinders (30 days, 450°C) in form of yellow-brown single crystals. The structure determination by four circle diffractometer data MoKα, 3 689 out of 3 689 Io(hkl), R = 4.22, Rw = 2.45) confirms the space group P21/c with lattice constants a = 687.7 pm; b = 3 118.5 pm; c = 686.4 pm; β = 119.3°; Z = 2. The characteristic feature of the structure is [In4O13]14- groups, oligomers consisting of four corner-sharing InO4 tetrahedra. These groups are connected by crystallographically distinct potassium atoms. The structure is isotypic with Na14[Al4O13] [2] and K14[Fe3O13] [3]. ECoN and MAPLE calculationes are discussed.
    Notes: Beim Tempern inniger Gemenge von K2O, CdO und elementarem In (Einwaageverhältnis 3,1:1,0:1,0) in verschlossenen Ag-Zylindern (30 Tage, 450°C) erhielten wir neben schwach roten Kristallen von K5InO4 [1] auch gelbbraune Kristalle von K14[In4O13]. Die Strukturaufklärung (Vierkreisdiffraktometerdaten, MoKα, 3 698 von 3 698 Io(hkl), R = 4,22%, Rw = 2,45%) erfolgte in der Raumgruppe P21/c mit den Gitterkonstanten: a = 687,7 pm; b = 3 118,5 pm; c = 686,4 pm; β = 119,3°; Z = 2. Charakteristischer Teil der Struktur sind „isolierte“ Baugruppen [In4O13]14-, die aus vier über Ecken verknüpften InO4-Tetraedern bestehen und durch kristallographisch unterschiedliche K+ in verschiedenen Richtungen verknüpft werden. Dieses Oxid ist isotyp zu Na14[Al4O13] [2] und K14[Fe4O13] [3]. Der Madelunganteil der Gitterenergie MAPLE wird berechnet und mit den binären Oxiden verglichen.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 620 (1994), S. 210-224 
    ISSN: 0044-2313
    Keywords: „Orthoindat“ K5[InO4] ; structure ; MAPLE ; VADI ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: A New „Orthoindate“ of an Alkali Metal: K5[InO4]Hitherto unknown K5[InO4] was prepared by heating intimate mixtures of K2O, In2O3 and elementar In (molar ratio 10.0 : 1.0 : 4.0) in closed Ni-cylinders (30 days, 500°C) in form of pale red, nearly colourless, transparent, single crystals. Same crystals were obtained by heating mixtures of K2O, CdO and elementar In (molar ratio 3.1 : 1.0 : 1.0) in closed Ag-cylinders (30 days, 450°C), too. In this case we also found yellow-brown crystals of K14[In4O13] [1]. Structure determination by four circle diffractometer data (MoKα, 15279 out 17454 Io(hkl), R = 5.60%, Rw = 5.25%). Space group P1 with a = 1827.9 pm; b = 1694.4 pm; c = 1329.4 pm; α = 113.3°; β = 111.4°; γ = 105.2°; Z = 16. Characteristic feature of the structure are isolated [InO4]5--tetraeder. The Madelung Part of Lattice Energy, MAPLE, the Mean Fictive Ionic Radii, MEFIR, Effective Coordination Numbers, ECoN, and Charge Distribution, VADI, are calculated.
    Notes: Beim Tempern inniger Gemenge von K2O, In2O3 und elementarem In (10,0 : 1,0 : 4,0) in verschlossenen Ni-Zylindern (30 Tage, 500°C) erhielten wir erstmals K5[InO4] als blaßrote, fast farblose, transparente Einkristalle. Gleichartige Kristalle erhielten wir auch beim Tempern von K2O, CdO und elementarem In (3,1 : 1,0 : 1,0) in verschlossenen Ag-Zylindern (30 Tage, 450°C). Neben den blaßroten Kristallen von K5[InO4] lagen in dieser Probe auch bernsteinfarbene Kristalle von ebenfalls vorher unbekanntem K14[In4O13] [1] vor. Die Strukaufklärung (Vierkreisdiffraktometerdaten, MoKα, 15279 von 17454 Io(hkl), R = 5,60%, Rw = 5,25%) erfolgte in der Raumgruppe P1 mit den Gitterkonstanten: a = 1827,9 pm; b = 1694,4 pm; c = 1329,4 pm; α = 113,28°; β = 111,39°; γ = 105,20°; Z = 16. Für die Struktur sind „isolierte“ [InO4]5--Tetraeder charakteristisch. Der Madelunganteil der Gitterenergie, MAPLE, die mittleren fiktiven Ionenradien, MEFIR, Effektive Koordinationszahlen, ECoN, sowie die Ladungsverteilung werden berechnet.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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