Biologic therapy for the treatment of malignant common epithelial tumors of the ovary

Abstract

There are a number of strategies to the treatment of gynecologic tumors that involve the use of biologic agents. Biologic agents may be immunologic in nature and act directly on the tumor or to boost an immune response to the tumor, or they may be nonimmune in nature and directly affect the tumor or a physiologic process on which the tumor depends. Although the potential for these agents in the treatment of all gynecologic tumors is great, most of the data to date have been generated in ovarian cancer. Clinical trials of alpha interferon administered intraperitoneally in patients with small volume ovarian cancer have revealed high response rates with acceptable toxicity. The mechanism of the antitumor effect (i.e., direct tumor killing vs. indirect boosting host immune response) has not yet been determined. Clinical trials of intraperitoneal lymphokine‐activated killer (LAK) cells plus recombinant interleukin‐2 have also been started based upon significant antitumor effects noted in xenogeneic systems. The finding that the peritoneal fluid of interferon‐treated patients is rich with monocytes and macrophages has led to the development of a clinical trial using intraperitoneal human monocytes activated with recombinant gamma interferon along with gamma interferon. Monoclonal antibodies have already made a significant impact on the diagnosis of ovarian cancer, and are being brought to clinical trial as therapeutic agents. The OC‐125 antigen is shed by ovarian tumor cells and its elevation in the serum of patients with undiagnosed pelvic masses is highly predictive for ovarian neoplasia. Furthermore, its persistence in the serum of patients with ovarian cancer during chemotherapy is nearly always associated with persistent disease. A number of monoclonal antibodies specific for ovarian cancer have been developed. Radiolabeled antibodies administered intralymphatically and intraperitoneally may be able to demonstrate the presence of tumor reliably enough to save some patients from second‐look laparotomy. In addition, clinical trials are underway using immunotoxins, antitumor antibodies conjugated to potent plant or bacterial toxins that are effective at killing cells with amazing efficiency. Antibodies conjugated to alpha‐emitting radioisotopes like astatine‐211 or to radioisotopes emitting gamma or beta waves or Auger electrons are candidates for clinical trial. There is also some interest in attempting to improve the therapeutic index by using antibodies conjugated to cytotoxic chemotherapeutic agents. It is also possible that an antibody would not need to be attached to another effector molecule if it were directed against a growth‐factor receptor or some other physiologically important target on the tumor cells. The integration of these approaches with more conventional treatment may be associated with an increase in complete remission rate and long‐term survival. Yet another biologic agent of particular interest in gynecologic neoplasms is Mullerian inhibiting substance (MIS). Since the genitourinary tr...

Overexpression of CD157 Contributes to Epithelial Ovarian Cancer Progression by Promoting Mesenchymal Differentiation

“…We chose OVCAR-3 ovarian cancer cells as the most suitable model for studying the effects induced by CD157 expression since they have an epithelial phenotype [24], are poorly invasive, scarcely motile on plastic and barely anchorage-independent [25]. To explore the biological significance of CD157 in ovarian cancer progression, we stably transfected full length CD157 in CD157-negative OVCAR-3 cells (Figure 1A).…”

Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells

“…In addition, NIH:OVCAR3 cells are non-invasive in Boyden chambers, poorly anchorage-independent, non-motile on plastic and do not invade in collagen gels (Hamilton et al , 1987). These properties make NIH:OVCAR3 cells ideally suitable to study EMT.…”

Ovarian cancer

“…Ovarian cancer is a suitable model for the evaluation of biological therapies. The disease is frequently localized to the peritoneal cavity, producing favorable pharmacodynamics for intraperitoneal administration of biological agents [75]. Furthermore, the peritoneal cavity can mount an inflammatory response and effector cells may be recruited to this site.…”