) We are studying the possibility of arresting the growth of ovarian cancer by increasing the expression of the major gene responsible for hereditary ovarian and breast cancer, breast cancer gene number 1 (BRCA1). Interestingly, defective expression of BRCA1 is also found in 70 percent of sporadic ovarian cancer, thus potentially making it an important component of carcinogenesis in both inherited and sporadic ovarian cancer. We had previously reported that gene transfer of BRCA1 into cancer cells inhibits growth and reduces tumorigenesis of human cancer cells in nude mice. In addition, BRCA1 appears to be a secreted growth inhibitor; secretion of BRCA1 by transduced tumor cells may effectively increase the growth suppression action of BRCA1 by pericrania mechanisms. The purpose of this study is to use disabled mortise retrovirus to transduce ovarian cancer cells with the BRCA1 gene and evaluate the effect on tumor growth in patients. Experiments in mice have shown that the transfer of BRCA1 gene into cancer cells using a retroviral vector results in a striking reduction in growth of cancer. In a preliminary phase I study of retroviral BRCA1 gene therapy in patients with metastatic ovarian cancer, we evaluated dosing, toxicity, and response to treatment. Toxicity was minimal, particularly when compared to cytotoxic chemotherapy, and one patient demonstrated a measurable response. Based on these findings, we propose a phase II trial to evaluate the potential efficacy of BRCA1 gene therapy in patients with ovarian cancer. Patients will undergo intraperitoneal infusion of retroviral BRCA1 therapy. Eligible patients will be those who have completed first-line surgery and chemotherapy and are candidates for second-look surgery or have recurrent disease and have measurable disease less than 3 cm.
| Tait, D L; Obermiller, P S; Holt, J T (2000) Preclinical studies of a new generation retroviral vector for ovarian cancer BRCA1 gene therapy. Gynecol Oncol 79:471-6 |
| Tait, D L; Obermiller, P S; Hatmaker, A R et al. (1999) Ovarian cancer BRCA1 gene therapy: Phase I and II trial differences in immune response and vector stability. Clin Cancer Res 5:1708-14 |
| Tait, D L; Obermiller, P S; Jensen, R A et al. (1998) Ovarian cancer gene therapy. Hematol Oncol Clin North Am 12:539-52 |
