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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinsk bioteknologi) ;pers:(Stigbrand T.)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinsk bioteknologi) > Stigbrand T.

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  • Erlandsson, Ann, et al. (författare)
  • In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives
  • 2006
  • Ingår i: Molecular Immunology 2006;42:599-604.
  • Tidskriftsartikel (refereegranskat)abstract
    • At immunolocalization of experimental tumors, idiotypic monoclonal antibodies, such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo terapeutics in the tumor. These carriers also remain in the circulation and may cause negative side-effects in other tissues.In this report, several derivatives of the antiidiotypic antibody anti-TS1 were produced and tested for their clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal anri-TS1, scFv of a anti-TS1 and anti-TS1 Fab and Fab'2 fragments were produced by recombinant technology or by cleavage with Ficin. The scFv was tailored by use of the variable domain genes of the light and heavy chain from the hybridoma clone in combination with a (Gly4Ser)3-linker, followed by expression in E. coli. When tested for clearing capacity, the intact divalent antiidiotypic IgG was found to be the most efficient. The divalent Fab'2 and the monovalent Fab fragment also demonstrated significant clearing, but lower than the intact antiidiotypic IgG. The anti-TS1 scFv antibody when injected separately was not found to clear the idiotype, but could do so when preincubated with the idiotype. Rapid excretion and in vivo instability of this lowmolecular weight antibody fragment may be the major reasons. Similar results were obtained when the system was reversed and the 131I-labeled antiidiotype IgG was cleared with the idiotype Fab'2 fragment. It is concluded that both intact antiidiotypic IgG, Fab'2 and Fab fragments are able to clear the idiotypic antibodies. The experimental data support the conclusion that the Fc parts from both the idiotype and the antiidiotype may contribute to this elimination
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  • Johansson, A, et al. (författare)
  • Epitope specificity of monoclonal anticytokeratin antibody TS1
  • 1999
  • Ingår i: Cancer Res 1999;59:45-51.
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to their abundance in epithelial cells and deposition in necrotic regions intratumorally, cytokeratins (CKs) have been established as valuable targets for both radioimmunolocalization and radioimmunotherapy. The target epitope for the monoclonal anti-CK8 antibody, TS1, used for both experimental radioimmunolocalization and radioimmunotherapy, was determined by means of synthesis of 96 overlapping peptides that covered the entire CK8 molecule. A highly conserved peptide sequence, spanning amino acids (aa) 343357 and covering the discontinuous epitope in the helical 2B domain, was identified. The epitope retains its helical structure, as shown with circular dichroism spectroscopy, although the length of the peptide (i.e., >20 aa) is crucial for maintenance of immunoreactivity. To determine which aa residues are crucial for binding to the monoclonal antibody, alanine scanning was performed on a 26-mer covering aa 340365, with the sequence RGELAIKDANAKLSELEAALQRAKQ. The 26 modified peptides were evaluated using ELISA and BIAcore technology. The uniqueness of this epitope has been established by data base sequence comparisons
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