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Local AdCD40L gene therapy is effective for disseminated murine experimental cancer by breaking T-cell tolerance and inducing tumor cell growth inhibition
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
2009 (English)In: Journal of immunotherapy (1997), ISSN 1524-9557, E-ISSN 1537-4513, Vol. 32, no 8, 785-792 p.Article in journal (Refereed) Published
Abstract [en]

CD40 ligand (CD40L) is one of the most potent stimulators of Th1-type   immunity through its maturation of dendritic cells that, in turn,   stimulate effector cells such as T cells and NK cells. Lately,   CD40-mediated cell growth inhibition and apoptosis have been in focus   for the development of novel cancer treatment regiments, including   recombinant soluble CD40L or CD40-stimulating antibodies. In this   study, intravesical CD40L gene transfer through adenoviral vectors   (AdCD40L) was used to treat an aggressive model of disseminated bladder   cancer (MB49/C57BL/6). Three weekly AdCD40L vector instillations   increased overall survival of tumor-bearing mice (mean 18.5 d, control   mice 13 d). Furthermore, bladder tumors were eradicated (2 of 10)   simultaneously as lung metastases (6 of 10) were cleared. FoxP3 levels   were similar in the tumors of AdCD40L-treated mice and control mice but   the tumor-infiltrating effector T cells in AdCD40L-treated mice were   cytotoxic (CD107a+) in contrast to those in control-treated tumors.   Furthermore, AdCD40L gene therapy could induce cell growth inhibition   and cell death in the MB49 tumor cells in vitro and in vivo. However,   this effect was not Potent enough to cure growing tumors in   immunodeficient mice. In conclusion, AdCD40L gene therapy is potent for   disseminated cancer both by activation of T cells and controlling tumor cell growth and viability.

Place, publisher, year, edition, pages
2009. Vol. 32, no 8, 785-792 p.
Keyword [en]
CD40L, immunotherapy, gene therapy, apoptosis, CD107a, FoxP3
National Category
Medical and Health Sciences
Research subject
Clinical Immunology
Identifiers
URN: urn:nbn:se:uu:diva-110784ISI: 000270321100002OAI: oai:DiVA.org:uu-110784DiVA: diva2:278338
Available from: 2009-11-25 Created: 2009-11-25 Last updated: 2017-12-12Bibliographically approved

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