Enhanced Targeted Therapy: Evaluating the Efficacy of BAY 79-4620 in CAIX-Positive Tumor Models

BAY 79-4620 is an innovative immunoconjugate, comprising a monoclonal antibody targeting the MN antigen (carbonic anhydrase IX; CAIX), which is coupled with the MMAE auristatin derivative. This compound is in Phase I trials and is notable for its selective action against various cancers, including gastric, lung, pancreatic, and colorectal, where CAIX is frequently overexpressed due to HIF-1α regulation. This overexpression is associated with increased tumor aggressiveness and a poorer prognosis.

The immunoconjugate has been evaluated for its pharmacological properties and has shown specific binding and internalization into CAIX-positive tumor cells in vitro. The MMAE component, which inhibits tubulin, induces mitotic arrest and selectively kills tumor cells with low nanomolar potency. In contrast, CAIX-negative cell lines only exhibit cytotoxicity at very high concentrations. The in vivo effectiveness of the conjugate was superior to free MMAE or an unconjugated antibody, with a minimum effective dose of 0.625mg/kg in a specific tumor model and a dosing schedule of every 4 days for three times. At lower doses, 80% of animals showed tumor regression, and higher doses led to complete eradication in 90% of cases. The treatment was less toxic than free MMAE, with a maximum tolerated dose in mice exceeding the lethal dose of MMAE.

Overall, the targeted delivery of MMAE via BAY 79-4620 has shown increased efficacy in models with elevated CAIX expression, positioning it as a promising candidate for treating various CAIX-positive cancers. The study was presented at the 101st Annual Meeting of the American Association for Cancer Research in 2010.