TY - JOUR T1 - Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth <em>In Vitro</em> JF - Anticancer Research JO - Anticancer Res SP - 4117 LP - 4128 DO - 10.21873/anticanres.13570 VL - 39 IS - 8 AU - NARASIMHA RAO UDA AU - FRANK STENNER AU - VOLKER SEIBERT AU - PETRA HERZIG AU - NORBERT MARKULY AU - MARC VAN DIJK AU - ALFRED ZIPPELIUS AU - CHRISTOPH RENNER Y1 - 2019/08/01 UR - http://ar.iiarjournals.org/content/39/8/4117.abstract N2 - 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. ER -