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

Narasimha Rao Uda1,2, Frank Stenner3,4, Volker Seibert5,6

  • 1Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland christoph.renner@unibas.ch narasimha.uda@unige.ch.

Anticancer Research
|August 2, 2019
PubMed
Abstract

Insights

Researchers developed a humanized carbonic anhydrase 12 (CA12) antibody, 4AG4, that inhibits cancer cell growth. This novel antibody targets CA12-positive tumors, offering a new therapeutic avenue.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Carbonic anhydrase 12 (CA12) is a membrane enzyme overexpressed in many human cancers.
  • High CA12 expression correlates with poor prognosis, making it a promising therapeutic target.
  • Developing targeted therapies against CA12 is crucial for effective cancer treatment.

Purpose of the Study:

  • To develop a humanized antibody targeting carbonic anhydrase 12 (CA12).
  • To evaluate the anti-cancer activity of the developed CA12-specific antibody.
  • To assess the antibody's potential as a therapeutic agent for CA12-positive tumors.

Main Methods:

  • Construction and screening of antibody libraries using Retrocyte display®.
  • Characterization of antibody binding and blocking activity via ELISA, flow cytometry, and enzymatic assays.
  • Assessment of spheroid viability using Cell-Titer-Fluor assay.

Main Results:

  • A novel humanized CA12-specific antibody, designated 4AG4, was successfully developed.
  • The 4AG4 antibody recognized CA12 and effectively blocked its enzymatic activity.
  • Significant inhibition of lung adenocarcinoma (A549) spheroid growth was observed in vitro, mediated by CA12 enzymatic blockade.
  • Comparable anti-tumor effects were achieved using CA12-gene knockout A549 cells.

Conclusions:

  • The newly developed humanized CA12-antibody (4AG4) demonstrates significant anti-cancer activity.
  • This antibody represents a novel therapeutic tool for targeting CA12-positive tumors.
  • Targeting CA12 enzymatic activity is a viable strategy for developing new cancer treatments.
Keywords:
Carbonic anhydrase 12cancerhypoxiatherapeutic antibodies

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