%0 Journal Article %A NARASIMHA RAO UDA %A FRANK STENNER %A VOLKER SEIBERT %A PETRA HERZIG %A NORBERT MARKULY %A MARC VAN DIJK %A ALFRED ZIPPELIUS %A CHRISTOPH RENNER %T Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro %D 2019 %R 10.21873/anticanres.13570 %J Anticancer Research %P 4117-4128 %V 39 %N 8 %X Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: Our newly identified humanized CA12-antibody with anti-cancer activity, represents a new tool for the treatment of CA12-positive tumors. %U https://ar.iiarjournals.org/content/anticanres/39/8/4117.full.pdf