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Nieken Karen Jule O’Brien Kathryn McDonnell Alexander Zhaunova Liudmila Ohkura Hiroyuki 《Chromosoma》2023,132(1):1-18
Chromosoma - In prophase of the first meiotic division, chromatin forms a compact spherical cluster called the karyosome within the enlarged oocyte nucleus in Drosophila melanogaster. Similar... 相似文献
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B. J. Kroesen J. Nieken D. T. Sleijfer G. Molema E. G. E. de Vries H. J. M. Groen W. Helfrich T. H. The N. H. Mulder L. de Leij 《Cancer immunology, immunotherapy : CII》1997,45(3-4):203-206
The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex,
as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2.
In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation
is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with
CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based
bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites
or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e.
intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas
no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab′)2 in combination
with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity
including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5–8 μg/kg. High plasma concentrations
of the inflammatory cytokines tumor necrosis factor α and interferon γ were observed at this dose. Whereas bsAb-dictated antitumour
activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses
were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low
systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal
residual disease.
Accepted: 14 October 1997 相似文献
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