Effect of TRA-8 anti-DR5 monoclonal antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.

Academic Article

Abstract

  • 14695 Background: It has been previously demonstrated that TRA-8 anti-DR5 monoclonal antibody induces apoptosis in primary human ovarian cancer (Gynecol Oncol 105:291-298, 2007). The purpose of this study was to evaluate the cytotoxicity of TRA-8 in combination with carboplatin and paclitaxel utilizing the same ex vivo three-dimensional tissue slice technique. METHODS: Primary epithelial ovarian cancer tissue from 18 patients was obtained at the time of cytoreductive surgery. The Krumdieck tissue slicer was used to prepare 5 mm slices. 300 μm thick slices were incubated in media and treated with TRA-8, carboplatin, paclitaxel, or a combination of TRA-8 plus carboplatin and paclitaxel for 24-48 hours. To evaluate cytotoxicity, ATP levels were assessed using a luminescence-based ATP assay and compared to untreated control slices. RESULTS: The average patient age was 63 years-old (range 48-84). Fourteen patients (78%) were Caucasian and 4 (22%) were African American. Sixteen (89%) tumor specimens were papillary serous and 2 (11%) were endometrioid histology. Ten specimens were treated with carboplatin and paclitaxel alone. A dose-response curve was demonstrated in 8 of 10 specimens. Eight specimens were treated with TRA-8 plus carboplatin and paclitaxel. Increased cytotoxicity with TRA-8 compared to chemotherapy alone was observed in 6 of 8 specimens. Specimens treated with 100 ng/mL of TRA-8 alone demonstrated 22% mean cytotoxicity. Specimens treated with carboplatin and paclitaxel showed 33% mean cytotoxicity. In specimens treated with carboplatin, paclitaxel, and TRA-8, mean cytotoxicity was 70%. The difference between TRA-8 plus chemotherapy and chemotherapy alone (p = 0.013), and the difference between TRA-8 plus chemotherapy and TRA-8 alone (p = 0.006) was significant. CONCLUSIONS: These data indicate that the combination of TRA-8 and chemotherapy results in more cytotoxicity in an ovarian cancer model than either treatment alone. The use of death receptor monoclonal antibodies such as TRA-8 may serve as a valuable adjuvant therapy for patients with ovarian cancer. [Table: see text].
  • Published In

    Author List

  • Frederick PJ; Kendrick JE; Straughn JM; Oliver PG; Lin H; Manna DLD; LoBuglio AF; Buchsbaum DJ
  • Start Page

  • 14695
  • Volume

  • 26
  • Issue

  • 15_suppl