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  • 1
    ISSN: 1432-0851
    Keywords: Anti-GD2 antibody ; Cytotoxic T cells ; Immunoconjugate ; Neuroblastoma ; Superantigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Superantigens such as the staphylococcal enterotoxin A (SEA) are among the most potent T cell activators known. They bind to major histocompatibility complex (MHC) class II molecules and interact with T cells depending on their T cell receptor (TCR) Vβ expression. Superantigens also induce a variety of cytokines and trigger a direct cytotoxic effect against MHC-class-II-positive target cells. In order to extend superantigen-dependent cell-mediated cytotoxicity (SDCC) to MHC-class-II-negative neuroblastoma cells, SEA was linked to the anti-ganglioside GD2 human/mouse chimeric monoclonal antibody (mAb) ch14.18. Ganglioside GD2 is expressed on most tumours of neuroectodermal origin but is expressed to a lesser extent on normal tissues. The linkage of ch 14.18 to SEA was achieved either with a protein-A-SEA fusion protein or by chemical coupling. Both constructs induced T-cell-mediated cytotoxicity towards GD2-positive neuroblastoma cells in an effector-to-target(E∶T)-ratio-and dose-dependent manner in vitro. To reduce the MHC class II affinity of SEA, a point mutation was introduced in the SEA gene (SEAm9) that resulted in 1000-fold less T cell killing of MHC-class-II-expressing cells as compared to native SEA. However, a protein-A-SEAm9 fusion protein mediated cytotoxicity similar to that of protein-A-SEA on ch14.18-coated, MHC-class-II-negative neuroblastoma cells. Taken together, these findings suggest that superantigen-dependent and monoclonal-antibody-targeted lysis may be a potent novel approach for neuroblastoma therapy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0851
    Keywords: Key words Anti-GD2 antibody ; Cytotoxic T cells ; Immunoconjugate ; Neuroblastoma ; Superantigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Superantigens such as the staphylococcal enterotoxin A (SEA) are among the most potent T cell activators known. They bind to major histocompatibility complex (MHC) class II molecules and interact with T cells depending on their T cell receptor (TCR) Vβ expression. Superantigens also induce a variety of cytokines and trigger a direct cytotoxic effect against MHC-class-II-positive target cells. In order to extend superantigen-dependent cell-mediated cytotoxicity (SDCC) to MHC-class-II-negative neuroblastoma cells, SEA was linked to the anti-ganglioside GD2 human/mouse chimeric monoclonal antibody (mAb) ch14.18. Ganglioside GD2 is expressed on most tumours of neuroectodermal origin but is expressed to a lesser extent on normal tissues. The linkage of ch14.18 to SEA was achieved either with a protein-A–SEA fusion protein or by chemical coupling. Both constructs induced T-cell-mediated cytotoxicity towards GD2-positive neuroblastoma cells in an effector-to-target(E:T)-ratio-and dose-dependent manner in vitro. To reduce the MHC class II affinity of SEA, a point mutation was introduced in the SEA gene (SEAm9) that resulted in 1000-fold less T cell killing of MHC-class-II-expressing cells as compared to native SEA. However, a protein-A–SEAm9 fusion protein mediated cytotoxicity similar to that of protein-A–SEA on ch14.18-coated, MHC-class-II-negative neuroblastoma cells. Taken together, these findings suggest that superantigen-dependent and monoclonal-antibody-targeted lysis may be a potent novel approach for neuroblastoma therapy.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 16 (2000), S. 249-252 
    ISSN: 1434-808X
    Keywords: Schlüsselwörter ; Artifizielle donogene Insemination • Rechtsfragen ; Keywords ; Artificial insemination from the donor • Legal aspects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Therapeutical inseminations from the donor take place in Germany for more than tens of years. The 73th German Phycians × Meeting has given consent in 1970. Today more than 60,000 to 70,000 children live in Germany born after fecundation by donor sperm. Selection of spermdonors takes place in aggreement to international criteria. The priciples of treatment of donogen insemination are in hand as recommendation. But some legal problems demand lawfull regulation for instance anonymity of the donor, law of family and successions, safe-keeping of documents, fees for the donor.
    Notes: Zusammenfassung Therapeutische donogene Inseminationen werden seit mehr als 3 Jahrzehnten in Deutschland durchgeführt. Der 73. Deutsche Ärztetag hatte 1970 seine Zustimmung gegeben. Heute leben in Deutschland mehr als 60.000–70.000 Kinder, die ihr Leben der Befruchtung mit Spendersperma verdanken. Die Auswahl der Spermaspender erfolgt nach international üblichen Kriterien. Es liegen Behandlungsgrundsätze für die donogene Insemination als Empfehlungen vor. Aber einige rechtliche Probleme wie Anonymität des Spenders, Familien- und Erbrecht, Verwahrfrist der Akten, Spenderhonorar bedürfen noch einer gesetzlichen Regelung.
    Type of Medium: Electronic Resource
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