ONCOmmunity

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

By: Narasimha Rao Uda, Frank Stenner, Volker Seibert, Petra Herzig, Norbert Markuly, Marc VAN Dijk, Alfred Zippelius, Christoph Renner

Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland christoph.renner@unibas.ch narasimha.uda@unige.ch.
2019-06-12; doi: 10.21873/anticanres.13570

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

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.