Potential Monoclonal Antibody Therapy for the Treatment of Ovarian Cancer

Although ovarian cancer is the fifth most common cancer among women, it causes more death than any other type of female reproductive cancer (Morch et al., 2009). Besides difficulties in early detection, limited options for the treatment of ovarian cancer at late stages have been the major cause of high mortality rate (Jemal et al., 2003). About 76% of women with ovarian cancer survive 1 year after diagnosis, but only about 45% will live 5 years after diagnosis (Choi et al., 2008). Therefore, it may be desirable to look for alternative means of treating this type of cancer rather than the conventional ones including chemoor radiotherapy. During the last two decades, target-oriented antibody-based anti-cancer drugs have become the main stream choices for cancer treatments in humans. Although the efficacy of cancer treatments varies greatly with individual cases, overall improvements of patients' care and survival are significant, when compared to those of the conventional ones. Besides those approved by the FDA of the United States of America for the clinical treatments of cancer, numerous antibody-drug candidates are still at various stages of clinical trials and pending for the final approval by the FDA (Waldmann, 2003). Generally speaking, the majority of antibody-based anti-cancer drugs are target-oriented and the adverse side effects upon infusion of the antibody drugs are relatively mild as compared to those of the traditional ones. Therefore, selections of suitable targets against the tumor cells have become an essential step for the long term antibody drug development. In general, the ideal tumor target for the antibody drugs can be selected based on its accessibility, high abundance and surface homogeneity. Moreover, it should not be highly expressed on normal cells or tissues, especially the vital organs in humans (McGuire et al., 1996). Recently, two monoclonal antibodies were identified and selected based on these criteria for ovarian cancer. One is RP215 which recognizes a carbohydrate-associated epitope found preferentially in cancer cell-expressed immunoglobulin superfamily proteins, designated in general as CA215. The other is GHR106 which was shown to react with the extracellular domain of human GnRH receptor. Both CA215 and GnRH receptor are widely expressed among cancer cells of different tissue origins, especially those of the human ovary with positive rates ranging from 60-80% (Lee et al., 2008, 2009; Lee & Ge,