Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model

Estes, Jacob M.; Oliver, Patsy G.; Straughn, J. Michael; Zhou, Tong; Wang, Wenquan; Grizzle, William E.; Alvarez, Ronald D.; Stockard, Cecil R.; LoBuglio, Albert F.; Buchsbaum, Donald J.

doi:10.1016/j.ygyno.2006.12.033

Cited by 40 publications

(38 citation statements)

References 31 publications

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“…TRAIL kills a variety of tumor cells, but importantly, has no or minimal effects on normal cells because TRAIL death receptors are expressed essentially only in transformed cells. Great excitement for the potential use of TRAIL for ovarian cancers was initially generated, as TRAIL or TRAIL agonists produced significant cytotoxicity in certain ovarian cancer cell lines and xenografts (Zhao et al, 1995;Estes et al, 2007;Duiker et al, 2009). TRAIL activation of the extrinsic apoptotic pathway occurs independently of p53 status, an important issue in ovarian cancer therapy, as many tumors possess p53 mutations, rendering them resistant to chemotherapy (Igney and Krammer, 2002).…”

Section: Sarkar and Fallermentioning

confidence: 99%

Telomere-Homologous G-Rich Oligonucleotides Sensitize Human Ovarian Cancer Cells to TRAIL-Induced Growth Inhibition and Apoptosis

Sarkar

Faller

2013

Nucleic Acid Therapeutics

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Section: Sarkar and Fallermentioning

confidence: 99%

Telomere-Homologous G-Rich Oligonucleotides Sensitize Human Ovarian Cancer Cells to TRAIL-Induced Growth Inhibition and Apoptosis

Sarkar

Faller

2013

Nucleic Acid Therapeutics

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“…Testing TRA-8 (apoptosis-inducing antibody) in ovarian cancer tissue slices showed a dose-response pattern, with the greatest cell killing at the highest TRA-8 concentration. However, there was considerable variability of sensitivity among 19 patients studied with IC 50 values of 6.0 to >1,000 ng/mL (22). With other tumors including breast and cervix, TRA-8 has shown additive and synergistic activity in conjunction with chemotherapy and/or radiation (20,23).…”

Section: Preclinical Modelsmentioning

confidence: 99%

Brief Overview of Preclinical and Clinical Studies in the Development of Intraperitoneal Radioimmunotherapy for Ovarian Cancer

Meredith

Buchsbaum

Alvarez

et al. 2007

Clinical Cancer Research

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Due to the generally slow and incomplete transit of i.p. infused agents into the circulation, treating disease confined to the peritoneal cavity with chemotherapy, biologics, and/or radionuclides provides a pharmacologic advantage. A higher i.p. concentration can be achieved than could be tolerated by systemic administration. An advantage of i.p. versus i.v. administration for localization of radiolabeled antibodies to small peritoneal surface disease has been shown in animal model and human biopsy studies (1, 2). A recent phase III Gynecologic Oncology Group chemotherapy trial has confirmed a survival advantage for i.p. delivery among women undergoing initial therapy for advanced ovarian cancer (3). Although the therapy was more difficult to tolerate such that 60% of patients randomized to the i.p. arm did not complete the entire regimen, there was a 16-month survival advantage. I.p. radionuclide therapy has been used in treatment of ovarian cancer for more than three decades, but side effects have been problematic in non^tumor-targeted 32 P therapy (4). Efforts to improve specificity have used a number of antigens expressed on ovarian cancer cells as targets for selective delivery of radionuclide-conjugates. Mouse models and cell culture have been prominent for preclinical study of agents and strategies in the development of i.p. targeted radionuclide therapy for ovarian cancer. Animal studies, which have directed clinical trials, have shown clear improvement in survival with various modifications including combination chemotherapy, pretargeting, and combination of antibodies over simply delivery of a radiolabeled antibody via i.p. route.

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“…These are currently in phase II evaluations in patients with advanced malignancies (38,39). In the present study, we used a DR5 agonistic antibody AD5-10 against TRAIL-resistant ovarian cancer cells, and our results shed light on the postulated critical role of DR5 and NK-mediated immunosurveillance in ovarian cancer progression.…”

Section: Discussionmentioning

confidence: 90%

Natural Immunity Enhances the Activity of a DR5 Agonistic Antibody and Carboplatin in the Treatment of Ovarian Cancer

El‐Gazzar

Perco

Eckelhart

et al. 2010

Molecular Cancer Therapeutics

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The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in cancer cells with little effect on normal cells. We have previously shown that TRAIL signaling is altered in most ovarian cancer patients and that resistance to TRAIL contributes to ovarian cancer progression. In this study, we investigated whether resistance to TRAIL may be overcome by a monoclonal TRAILR2 (DR5) agonistic antibody (AD5-10). We found that the joint presence of AD5-10 with TRAIL and natural killer (NK) cells expressing TRAIL resensitizes ovarian cancer cells to apoptosis in vitro and in vivo, respectively. The combination of AD5-10 with carboplatin exerts a more than additive effect in vitro, which may at least partially be explained by the fact that carboplatin triggers DR5 expression on ovarian cancer cells. Moreover, AD5-10 restores the sensitivity of platin-resistant ovarian cancer to carboplatin in vivo. In addition, we found that TRAIL expression and NK cells are abundant in the tumor microenvironment and that depletion of NK cells abolishes the antitumor activity of AD5-10. This indicates that NK-mediated immunosurveillance against ovarian cancer might be mediated by TRAIL and that apoptosis induced by AD5-10 requires the presence of NK cells. In conclusion, this study indicates a key role and strong antitumorigenic effect of DR5 and highlights a novel link between NK-mediated immunosurveillance and activation of DR5-mediated apoptosis in ovarian cancer. Mol Cancer Ther; 9(4); 1007-18. ©2010 AACR.

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Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model

Cited by 40 publications

References 31 publications

Telomere-Homologous G-Rich Oligonucleotides Sensitize Human Ovarian Cancer Cells to TRAIL-Induced Growth Inhibition and Apoptosis

Telomere-Homologous G-Rich Oligonucleotides Sensitize Human Ovarian Cancer Cells to TRAIL-Induced Growth Inhibition and Apoptosis

Brief Overview of Preclinical and Clinical Studies in the Development of Intraperitoneal Radioimmunotherapy for Ovarian Cancer

Natural Immunity Enhances the Activity of a DR5 Agonistic Antibody and Carboplatin in the Treatment of Ovarian Cancer

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