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Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro.
Anticancer Res 2019; 39(8):4117-4128AR

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®. 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.

Authors+Show Affiliations

Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland christoph.renner@unibas.ch narasimha.uda@unige.ch. School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Geneva, Switzerland.Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Division of Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.Agenus Inc. USA (4-Antibody AG), Basel, Switzerland. Lonza AG, Visp, Switzerland.Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Cureab GmbH, Riehen, Switzerland.Agenus Inc. USA (4-Antibody AG), Basel, Switzerland. AgenTus Therapeutics, Cambridge, U.K.Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Division of Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland christoph.renner@unibas.ch narasimha.uda@unige.ch.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31366496

Citation

Uda, Narasimha Rao, et al. "Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth in Vitro." Anticancer Research, vol. 39, no. 8, 2019, pp. 4117-4128.
Uda NR, Stenner F, Seibert V, et al. Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro. Anticancer Res. 2019;39(8):4117-4128.
Uda, N. R., Stenner, F., Seibert, V., Herzig, P., Markuly, N., VAN Dijk, M., ... Renner, C. (2019). Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro. Anticancer Research, 39(8), pp. 4117-4128. doi:10.21873/anticanres.13570.
Uda NR, et al. Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth in Vitro. Anticancer Res. 2019;39(8):4117-4128. PubMed PMID: 31366496.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth In Vitro. AU - Uda,Narasimha Rao, AU - Stenner,Frank, AU - Seibert,Volker, AU - Herzig,Petra, AU - Markuly,Norbert, AU - VAN Dijk,Marc, AU - Zippelius,Alfred, AU - Renner,Christoph, PY - 2019/06/12/received PY - 2019/07/02/revised PY - 2019/07/03/accepted PY - 2019/8/2/entrez PY - 2019/8/2/pubmed PY - 2019/8/8/medline KW - Carbonic anhydrase 12 KW - cancer KW - hypoxia KW - therapeutic antibodies SP - 4117 EP - 4128 JF - Anticancer research JO - Anticancer Res. VL - 39 IS - 8 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. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/31366496/Humanized_Monoclonal_Antibody_Blocking_Carbonic_Anhydrase_12_Enzymatic_Activity_Leads_to_Reduced_Tumor_Growth_In_Vitro_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=31366496 DB - PRIME DP - Unbound Medicine ER -