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.…
Author: | Sebastian F. M. Häusler, Itsaso Montalbán del Barrio, Joachim Diessner, Roland G. Stein, Jenny Strohschein, Arnd Hönig, Johannes Dietl, Jörg Wischhusen |
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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: | https://pubmed.ncbi.nlm.nih.gov/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): | CC BY: Creative-Commons-Lizenz: Namensnennung |