Feb 8, 2011

Generation and characterization of the first inhibitory antibody targeting tumour-associated carbonic anhydrase XII

Cancer Immunology, Immunotherapy : CII
Christina BattkeReinhard Zeidler

Abstract

The carbonic anhydrases (CAs) constitute a family of almost ubiquitous enzymes of significant importance for many physiological and pathological processes. CAs reversely catalyse the conversion of CO(2) + H(2)O to HCO(3) (-) and H(+), thereby contributing to the regulation of intracellular pH. Above all, CAs are of key importance for cells that perform glycolysis that inevitably leads to the intracellular accumulation of lactate. CA XII is a plasma membrane-associated isoform of the enzyme, which is induced by hypoxia and oestrogen and, consequently, expressed at high levels on various types of cancer and, intriguingly, on cancer stem cells. The enzyme is directly involved in tumour progression, and its inhibition has an anti-tumour effect. Apart from its role in carcinogenesis, the enzyme contributes to various other diseases like glaucoma and arteriosclerotic plaques, among others. CA XII is therefore regarded as promising target for specific therapies. We have now generated the first monoclonal antibody (6A10) that binds to the catalytic domain of CA XII on vital tumour cells and inhibits CA XII enzyme activity at nanomolar concentrations and thus much more effective than acetazolamide. In vitro results demonstrate that inhi...Continue Reading

  • References49
  • Citations28

Mentioned in this Paper

Monoclonal Antibodies
Tumor Cells, Uncertain Whether Benign or Malignant
Flow Cytometry
Immunofluorescence Assay
Lactate
Enzymes, antithrombotic
Immunologic Adjuvants
Adjuvant
Protoplasm
Neoplasms

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