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  • 1
    Electronic Resource
    Electronic Resource
    In vitro and in vivo antitumour activity of a chimeric anti-CD19 antibody (1995)
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 53-60 
    Details
    ISSN: 1432-0851
    Keywords: Key words Monoclonal antibody ; CD19 ; Immunoconjugate ; Chimeric antibody ; Lymphoma ; Idarubicin ; Immunochemotherapy ; Anti-CD19
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mouse monoclonal antibodies to CD19 detect an antigenic determinant expressed exclusively on the surface of B lymphocytes, and have previously been shown to be potentially useful therapeutic reagents for human B cell lymphoma. We report the production and characterization of a mouse/human chimeric antibody, cCD19, with potent in vivo antitumour activity. The genes encoding the variable domains for heavy (VH) and light (VL) chains were subcloned into eukaryotic expression vectors containing human constant region genes (IgG1 and κ), and co-transfected into non-secreting Sp2/0 mouse myeloma cells. Intraperitoneal administration of cCD19 produced inhibition of growth of subcutaneous CD19+ Sultan human B lymphoma tumours in scid/scid mice. When the antibody was administered 18 and 20 days after subcutaneous tumour inoculation, an approximately 30% reduction in tumour size was noted by day 29. cCD19 faithfully mimicked the in vitro binding characteristics of mCD19 as (a) the chimeric antibody was shown by flow cytometry to bind exclusively to cell lines that expressed CD19, (b) cCD19 was able to inhibit the binding of mCD19 on CD19+ cells completely and (c) the affinity of binding of the two antibodies was not significantly different [K a=(2.03±1.5)×108]. In bio-distribution studies, up to 14.8% of the total injected antibody dose per gram of tissue was localized in CD19+ Sultan tumours at 24 h approximately, 14.4% was present in the tumors at 48 h, and about 13.7% at 72 h. These levels were comparable to mCD19 administered in the same fashion. cCD19 conjugated to idarubicin was specifically and strongly cytotoxic to CD19+ cells cultured in vitro, and demonstrated an IC50 of 0.17 μM, similar to that of mCD19 (0.32 μM) and approximately 14-fold greater than the IC50 of free idarubicin. The specific cytotoxic capacity of cCD19 and its likely reduced immunogenicity suggest that it may potentially be of use in the treatment of refractory B cell lymphoma in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01788960
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Comparison of the biological properties of two anti-mucin-1 antibodies prepared for imaging and therapy (1997)
    Springer
    Cancer immunology immunotherapy 44 (1997), S. 323-328 
    Details
    ISSN: 1432-0851
    Keywords: Key words Anti-mucin-1 antibodies ; Imaging ; Biological properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A comparison was made between the murine anti-MUC1 antibody BC2 (which reacts with the peptide epitope APDTR) and the “humanised” antibody hCTMO1 from CellTech, which reacts with the MUC1 epitope RPAP. Preliminary studies demonstrated that hCTMO1 was a “good” antibody whereas BC2 was not. Various parameters were determined and conclusions reached. (a) Affinity: the affinity of hCTMO1 was 2.60×107M–1 and that of BC2 was 1.36×107M–1; we did not consider these numbers to be substantially different, although hCTMO1 was clearly of higher affinity than BC2. (b) On/off rate at 4°C: both antibodies bound effectively to the MUC-1 transfectant MOR5-CF2; the association rate for hCTMO1 was 3.8 times that of BC2 and the dissociation rate for BC2 was twice as fast as that of hCTMO1. (c) On/off rates at 37°C: at 37°C the association rate for hCTMO1 was greater than that of BC2. (d) Internalization: hCTMO1 was also more efficient at internalising bound antibody; 70% of bound hCTMO1 was internalised, whilst 6% of bound BC2 was internalised. From these studies it was clear that, while hCTMO1 was of similar affinity to BC2, the faster uptake and internalisation and lower off rate indicated that it was likely to be a superior antibody; this was proven in vivo. (e) Localisation: hCTMO1 bound much better in vivo than BC2 (68% compared to 28%). (f) Therapeutic experiments: BC2-idarubicin conjugates were essentially ineffective in eradicating tumours in mice whereas hCTMO1-idarubicin had a dramatic effect on breast cancer tumour cells growing in mice. We conclude that the simple measurements on/off rates and internalisation at 37°C are the most important parameters to use to determine antibody effectiveness, prior to embarking on clinical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050389
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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