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ID 34950
file
creator
Okawaki, Makoto
Yamaguchi, Yoshiyuki
Okita, Riki
Ohara, Masahiro
subject
Regulatory T cells
CD25
Basiliximab
Malignant effusion
OK-432
NDC
Medical sciences
abstract
Effects of low-dose anti-CD25 antibody on targeting regulatory T (Treg) cells in vitro and in vivo were investigated. Human-mouse chimeric anti-CD25 monoclonal antibody basiliximab was administered into the effusion cavity, followed by locoregional immunotherapy using OK-432 on day 7. Peripheral blood mononuclear cells and effusion lymphocytes (ELs) were collected before and after the basiliximab administration and subjected to further investigations. Surface phenotypes, IFN-y production, cytotoxic activity and foxp3 expression of ELs were assessed by flow cytometry, ELISA, 51Cr-releasing assay, and RT-PCR analysis, respectively. We observed that a low concentration of 0.01 μg/ml basiliximab effectively targeted CD4+CD25bri Treg cells while preserving CD4+CD25tlim activated T cells in vitro. This concentration of basiliximab significantly augmented interferon (IFN)- y production of ELs when interleukin (IL)-2 was added on day 0 or on day 1 after basiliximab. In the clinical study, intracavitary administration of basiliximab on day 0 followed by OK-432 on day 7 was as safe, well-tolerated, and effective as using OK-432 alone, and a low-dose of 0.002-0.005 mg/kg basiliximab could target CD4+CD25bri cells for at least 3 days while relatively preserving CD4 +CD25tlim cells. Foxp3 expression of ELs was not changed definitely by the intracavitary basiliximab. These results suggest that low-dose basiliximab can target Treg cells in vitro and in vivo, and subsequently augment the activation of ELs. Locoregional immunotherapy of malignant effusion using the Treg cell-conditioning regimen with low-dose basiliximab followed by OK-432 administration on day 0 or on day 1 should be evaluated for clinical efficacy in the next phase II trial.
journal title
Hiroshima Journal of Medical Sciences
volume
Volume 57
issue
Issue 1
start page
37
end page
46
date of issued
2008-03
publisher
Hiroshima University Medical Press
issn
0018-2052
ncid
language
eng
nii type
Departmental Bulletin Paper
HU type
Departmental Bulletin Papers
DCMI type
text
format
application/pdf
text version
publisher
rights
(c) Hiroshima University Medical Press.
department
Research Institute for Radiation Biology and Medicine
Graduate School of Biomedical Science
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