G250: A carbonic anhydrase IX monoclonal antibody

Abstract

G250 or carbonic anhydrase IX (CA IX) is a membrane-associated carbonic anhydrase (CA) thought to play a role in the regulation of cell proliferation in response to hypoxic conditions and may be involved in oncogenesis and tumor progression. G250 refers to a monoclonal antibody (mAb) that was raised by immunization of mice with human renal cell carcinoma (RCC) homogenates. The RCC-associated transmembrane protein designated G250 has since proven to be identical to tumor-associated protein MN or CA IX. Previous studies using a mAb against CA IX have shown that CA IX is induced constitutively in certain tumor types, but is absent in most normal tissues with the exception of epithelial cells of the gastric mucosa. Furthermore, previous immunobiochemical studies of malignant and benign renal tissues revealed that CA IX was also highly expressed in RCC. Studies on tumor-bearing kidneys demonstrate selective uptake of mAb CA IX in antigen-positive cells versus antigen-negative cells. Furthermore, extraordinarily high uptake and the requirement of a low protein dose to obtain tumor saturation with respect to tumor targeting occur with mAb CA IX. These studies formed the basis of numerous clinical trials aimed at mAb-guided therapy in patients with metastatic RCC.