@article {UDA4117, author = {NARASIMHA RAO UDA and FRANK STENNER and VOLKER SEIBERT and PETRA HERZIG and NORBERT MARKULY and MARC VAN DIJK and ALFRED ZIPPELIUS and CHRISTOPH RENNER}, title = {Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro}, volume = {39}, number = {8}, pages = {4117--4128}, year = {2019}, doi = {10.21873/anticanres.13570}, publisher = {International Institute of Anticancer Research}, abstract = {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{\textregistered}. 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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/39/8/4117}, eprint = {https://ar.iiarjournals.org/content/39/8/4117.full.pdf}, journal = {Anticancer Research} }