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Am J Transl Res. 2014 Jan 15;6(2):129-39. eCollection 2014.

Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion.

Author information

1
Department of Obstetrics and Gynecology, School of Medicine, University of Würzburg Josef-Schneider-Strasse 4, Germany ; Interdisciplinary Center for Clinical Research, School of Medicine, University of Würzburg Josef-Schneider-Strasse 4, Germany.
2
Department of Obstetrics and Gynecology, School of Medicine, University of Würzburg Josef-Schneider-Strasse 4, Germany.
3
Department of Obstetrics and Gynecology, School of Medicine, University of Würzburg Josef-Schneider-Strasse 4, Germany ; Else-Kröner Research Programm for Interdisciplinary Translational Immunology, School of Medicine, University of Würzburg Josef-Schneider-Strasse 4, Germany.

Abstract

The ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the A2A adenosine receptor (ADORA2A) on T and NK cells. The current study investigates the potential therapeutic use of the specific anti CD39- and anti CD73-antibodies A1 (CD39) and 7G2 (CD73) as these two ectonucleotidases are overexpressed in ovarian cancer (OvCA). As expected, NK cell cytotoxicity against the human ovarian cancer cell lines OAW-42 or SK-OV-3 was significantly increased in the presence of A1 or 7G2 antibody. While this might partly be due to antibody-dependent cell-mediated cytotoxicity, a luciferase-dependent assay for quantifying biologically active adenosine further showed that A1 and 7G2 can inhibit CD39 and CD73-dependent adenosine-generation. In turn, the reduction in adenosine levels achieved by addition of A1 and 7G2 to OAW-42 or SK-OV-3 cells was found to de-inhibit the proliferation of CD4(+) T cells in coculture with OvCA cells. Likewise, blocking of CD39 and CD73 on OvCA cells via A1 and 7G2 led to an increased cytotoxicity of alloreactive primed T cells. Thus, antibodies like A1 and 7G2 could improve targeted therapy in ovarian cancer not only by specifically labeling overexpressed antigens but also by blocking adenosine-dependent immune evasion in this immunogenic malignancy.

KEYWORDS:

CD39; CD73; Ovarian cancer; adenosine; immune escape

PMID:
24489992
PMCID:
PMC3902223

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