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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-120016
  • The ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the \(A_{2A}\) 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 thisThe ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the \(A_{2A}\) 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.show moreshow less

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Metadaten
Author: Sebastian F. M. Häusler, Itsaso Montalbán del Barrio, Joachim Diessner, Roland G. Stein, Jenny Strohschein, Arnd Hönig, Johannes Dietl, Jörg Wischhusen
URN:urn:nbn:de:bvb:20-opus-120016
Document Type:Journal article
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Language:English
Parent Title (English):American Journal of Translational Research
ISSN:1943-8141
Year of Completion:2014
Volume:6
Issue:2
Pagenumber:129–139
Source:American Journal of Translational Research 2014;6(2):129-139
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=PMC3902223
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 618 Gynäkologie, Geburtsmedizin, Pädiatrie, Geriatrie
Tag:CD39; CD73; adenosine; immune escape; ovarian cancer
Release Date:2015/11/26
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung