KAAG1 - A new target expressed in greater than 90% of ovarian tumors
Alethia’s most promising target in this indication, KAAG1, is an antigen that is expressed at the surface of ovarian cancer epithelial cells in greater than 85% of malignant tumors. Ovarian tumors are predominantly epithelial in origin and the pathology of these tumors is complex and is comprised of many types. Serous and endometrioid tumors make up the bulk of EOCs and a smaller percentage of cases present with clear cell or mucinous tumors. Very high expression of KAAG1 protein is detectable in ovarian tumors of all origins. Moreover, under normal conditions, KAAG1 is found in very few tissues underscoring its high degree of ovarian cancer specificity.
A mAb for controlling the spread of recurrent ovarian cancer
Cell-based validation in well-established models of ovarian cancer strongly suggested that KAAG1 contributed to the malignant character of several ovarian cancer cell lines. These in vitro results were substantiated in animal models of recurrent ovarian cancer which demonstrated that an IgG1 mAb specific for KAAG1 could significantly reduce the number of micro-metastatic tumors. This result was in complete agreement with results showing that the the lead mAb AB-3D3 could mediate effector functions such as antibody-dependent cell cytotoxicity (ADCC). Indeed, the combined results from the in vitro and in vivo studies indicate that over-expression of KAAG1 in ovarian tumors might contribute to increasing the malignant and invasive character of ovarian cancer cells.
The vast majority of ovarian cancer patients are diagnosed at late stages of the disease and despite aggressive surgical and chemotherapeutic treatments, recurrence is the leading cause of decreased overall survival. Very few mAbs against true ovarian cancer-specific targets are currently under development. The identification of KAAG1 and the ability of specific mAbs directed to this antigen to reduce the spread of ovarian tumors in vivo represents a promising therapeutic strategy with tremendous potential to address this important clinical need.
