Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro

Carbonic anhydrase 12 (CA12) is a membrane-associated enzyme that is highly expressed on many human cancers. It is a poor prognostic marker and hence an attractive target for cancer therapy. This study aimed to develop a humanized CA12-antibody with anti-cancer activity. Antibody libraries were cons...

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Published inAnticancer research Vol. 39; no. 8; pp. 4117 - 4128
Main Authors Uda, Narasimha Rao, Stenner, Frank, Seibert, Volker, Herzig, Petra, Markuly, Norbert, VAN Dijk, Marc, Zippelius, Alfred, Renner, Christoph
Format Journal Article
LanguageEnglish
Published Greece International Institute of Anticancer Research 01.08.2019
Subjects
Adenocarcinoma
Antibody libraries
Anticancer properties
Antigens
Cancer
Carbonic anhydrase
Carbonic anhydrases
Enzymatic activity
Enzyme-linked immunosorbent assay
Flow cytometry
Lung cancer
Lungs
Monoclonal antibodies
Tumors
Viability
Carbonic anhydrase 12
hypoxia
cancer
therapeutic antibodies
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Summary:Carbonic anhydrase 12 (CA12) is a membrane-associated enzyme that is highly expressed on many human cancers. It is a poor prognostic marker and hence an attractive target for cancer therapy. This study aimed to develop a humanized CA12-antibody with anti-cancer activity. Antibody libraries were constructed and screened by the Retrocyte display®. Antibody binding and blocking properties were determined by ELISA, flow cytometry and enzymatic activity assays. Spheroid viability was determined by Cell-Titer-Fluor assay. We developed a novel humanized CA12-specific antibody, 4AG4, which recognized CA12 as an antigen and blocked CA12 enzymatic activity. Our humanized CA12-antibody significantly inhibited spheroid growth of lung adenocarcinoma A549-cells in vitro by blocking CA12 enzymatic activity. Similar anti-tumor effects were recapitulated with CA12-gene knockout of A549-cells. Our newly identified humanized CA12-antibody with anti-cancer activity, represents a new tool for the treatment of CA12-positive tumors.
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ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.13570