SOLUBLE FORM OF CARBONIC ANHYDRASE IX (S-CA-IX), ASSAYS TO DETECT S-CA IX AND CA IX'S COEXPRESSION WITH HER-2/NEU/C-ERBB-2, AND CA IX-SPECIFIC MONOCLONAL ANTIBODIES TO NON-IMMUNODOMINANT EPITOPES

摘要

Disclosed herein among other MN/CA IX-related inventions are new MN/CA IX- specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Subsets of the new antibodies are to either the proteoglycan-like (PG) domain or to the carbonic anhydrase (CA) domain of MN/CA IX, and method s are provided by which antibodies can be prepared to the other MN/CA IX domains. 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, fragmen ts 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 I X (s-CA IX) in body fluids, alone but preferably in combination with antibodie s specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.