Cancer Immunology, Immunotherapy

, Volume 60, Issue 5, pp 649–658 | Cite as

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

  • Christina Battke
  • Elisabeth Kremmer
  • Josef Mysliwietz
  • Gabor Gondi
  • Claudia Dumitru
  • Sven Brandau
  • Stephan Lang
  • Daniela Vullo
  • Claudiu Supuran
  • Reinhard Zeidler
Original article


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 CO2 + H2O to HCO3 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 inhibition of CA XII by 6A10 inhibits the growth of tumour cells in 3-dimensional structures. In conclusion, we generated the first specific and efficient biological inhibitor of tumour-associated CA XII. This antibody may serve as a valuable tool for in vivo diagnosis and adjuvant treatment of different types of cancer.


Carbonic anhydrase Monoclonal antibody Cancer treatment Hypoxia Warburg effect 



Carbonic anhydrases

Supplementary material

262_2011_980_MOESM1_ESM.pdf (593 kb)
Supplementary material 1 (PDF 593 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Christina Battke
    • 1
  • Elisabeth Kremmer
    • 2
  • Josef Mysliwietz
    • 2
  • Gabor Gondi
    • 1
  • Claudia Dumitru
    • 3
  • Sven Brandau
    • 3
  • Stephan Lang
    • 3
  • Daniela Vullo
    • 4
  • Claudiu Supuran
    • 4
  • Reinhard Zeidler
    • 5
  1. 1.Department of Gene VectorsHelmholtz-CenterMunichGermany
  2. 2.Institute of Molecular ImmunologyHelmholtz-CenterMunichGermany
  3. 3.ENT-DepartmentUniversitätsklinikum EssenEssenGermany
  4. 4.Laboratorio di Chimica BioinorganicaUniversità degli Studi di FirenzeSesto Fiorentino (Firenze)Italy
  5. 5.ENT-DepartmentLudwig-Maximilians-UniversityMunichGermany

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