Development of Claudin MAbs for Treating Solid Tumors

ABSTRACT Solid tumors lead to 580,000 deaths annually in the US, and safe and effective therapeutics for many late- stage solid tumors are lacking. Ovarian cancer alone kills 14,000 people each year, and many patients do not respond to currently available treatments. The tight junction protein Claudin 6 (CLDN6) is a validated therapeutic target for many solid tumor types, including ovarian, endometrial, testicular, gastric, and pancreatic cancer. CLDN6 is differentially expressed on cancer cells with almost no expression in normal, healthy tissue. Despite being an attractive target, therapeutic MAbs targeting CLDN6 are difficult to discover due to an absolute need for high specificity. There are 26 human CLDN family members in total and most are broadly expressed and highly conserved, making drug specificity when targeting the CLDNs critically important but especially challenging. The extracellular region of CLDN6 closely resemble the widely expressed CLDN9 (3 amino acids different). The few CLDN6 MAbs discovered by others have demonstrated significant binding to other CLDN family members and most have now been halted in development. Here, we will develop a CLDN6 therapeutic for solid tumors.