Institute of Virology of the Slovak Academy of Sciences

Institute of Virology

Miriam Zatovicova

Jaromir Pastorek

Silvia Pastorekova

Jan Zavada

Marta Ortova Gut

Zuzanna Zavadova

Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) found in body fluids, such as, urine and serum. Soluble CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons. Diagnostic/prognostic methods for precancer/cancer that detect or detect and quantitate s-CA IX in body fluids, are described. Also disclosed is the coexpression of CA IX and HER-that provides potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer/cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, useful diagnostically/prognostically and therapeutically for cancer/precancer. Preferred are new antibodies, specific for non-immunodominant epitopes of MN/CA IX, are useful to detect soluble CA IX (s-CA IX) in body fluids, preferably in combination with antibodies specific to immunodominant epitopes of MN/CA IX.

Soluble form of carbonic anhydrase IX (s-CA IX), assays to detect s-CA IX, CA IX'S coexpression with HER-2/neu/c-erbB-2, and CA IX-specific monoclonal antibodies to non-immunodominant epitopes

Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) in body fluids, such as, urine and serum. Said s-CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons (kd) upon Western blot. A smaller s-CA IX form of about 20 to about 30 kd comprising the CA domain or parts thereof, not linked to the PG domain, has also been found in body fluids. Diagnostic/prognostic methods for precancer and cancer that detect or detect and quantitate said s-CA IX in body fluids, are described. Also disclosed herein is the coexpression of CA IX and HER-2/neu/c-erbB-2 that provides parallel, alternative and potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer and cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.

Soluble form of carbonic anhydrase IX (s-CA IX), assays to detect s-CA IX, CA IX's coexpression with HER-2/neu/c-erbB-2, and CA IX-specific monoclonal antibodies to non-immunodominant epitopes

Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) found in body fluids, such as, urine and serum. Soluble CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons. Diagnostic/prognostic methods for precancer/cancer that detect or detect and quantitate s-CA IX in body fluids, are described. Also disclosed is the coexpression of CA IX and HER-2 that provides potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer/cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, useful diagnostically/prognostically and therapeutically for cancer/precancer. Preferred are new antibodies, specific for non-immunodominant epitopes of MN/CA IX, useful to detect soluble CA IX (s-CA IX) in body fluids, preferably in combination with antibodies specific to immunodominant epitopes of MN/CA IX.

Soluble form of carbonic anhydrase IX (S-CA IX), assays to detect s-CA IX, CA IX'S coexpression with HER-2/NEU/C-ERBB-2, and CA IX-specific monoclonal antibodies to non-immunodominant epitopes

Growing community of inventors

Bratislava, Slovakia

Miriam Zatovicova