The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

Abstract

Abstract.The prognosis for patients with ovarian cancer is still poor and more effective therapeutic modalities are needed. (Radio)immunotherapy using monoclonal antibodies (Mabs) could be one of these approaches. Here, we review the status of (radio)immunotherapy using Mabs for the treatment of ovarian cancer. The Pubmed database was searched for clinical trials investigating the effect of (radio)immunotherapy in ovarian cancer published until October 1, 2007. Keywords for the search were: ovarian cancer, monoclonal antibodies, CA 125, gp38, HER2, HMFG, MUC1, TAG 72 and VEGF. A total of 44 trials on immunotherapy with unconjugated Mabs, Mab vaccination and (radio)immunotherapy directed towards the antigens CA 125, gp38, HER2, MUC1, TAG 72 or VEGF in patients with ovarian cancer were found, reviewed and discussed. Out of these trials, 23 studied immunotherapy with unconjugated Mabs, 5 vaccination with Mabs and 16 trials studied (radio)immunotherapy. The lack of large randomized prospective trials with Mabs directed to tumor-associated antigens expressed on ovarian cancer cells preclude any firm conclusion on the potential of Mabs use in the treatment of ovarian cancer. Oregovomab, directed against CA 125, and bevacizumab, targeting VEGF, are two unconjugated Mabs closest to clinical introduction for the treatment of ovarian cancer. Vaccination with Mab ACA 125 seems promising but these findings need to be confirmed in controlled randomized trials. Sole RIT should be investigated with the appropriate radionuclide and a Mab with high affinity for the specific tumor-associated antigen in the appropriate patient group to determine whether it may have a therapeutic effect. Additionally, appending (radio)immunotherapy with anti-TAG 72 or anti-MUC1 to other treatment strategies such as chemotherapy could also be a strategy worthwhile investigating. The potential of Mabs to complement current treatment paradigms, is encouraging and may bring a significant improvement to the overall therapeutic outcomes currently being achieved in ovarian cancer. IntroductionOvarian cancer is the fourth leading cause of cancer-related death in women, and accounts for the highest mortality rate of all gynecological malignancies (1). Its poor prognosis is mainly the result of the clinically occult nature of this disease. The peritoneal cavity in which the ovaries are localized provides a perfect environment for undisturbed subclinical growth. Furthermore, early detection is difficult because of the general asymptomatic presentation of the disease (2). In the majority (68%) of the patients, ovarian cancer is diagnosed with at least extensive abdominal spread (3). Standard treatment for advanced stage ovarian cancer is tumor debulking surgery and adjuvant chemotherapy. Although most ovarian cancers are sensitive to platinumbased chemotherapy, the prognosis remains poor. The 5-year INTERNATIONAL JOURNAL OF ONCOLOGY 32: 1145-1157 The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (Review) Abbreviations: ADCC, anti...