Gene therapy for the treatment of metastatic breast cancer by in vivo transduction with breast-targeted retroviral vector expressing antisense c-fos rna

Although murine retroviral vectors can transduce diverse types of proliferating cells, inclusion of tissue-specific or inducible promoters within retroviral vectors should theoretically target expression to allow selective expression within tumor cells. The mouse mammary tumor virus (MMTV) long terminal repeat (LTR) is expressed at high levels in only certain tissues in vivo: breast, prostate, salivary gland. We have employed these vectors to transduce MCF-7 human breast cancer cells. Transduction of cultured cells by supernatants from cloned producer cells expressing either antisense c-fos RNA or antisense c-myc RNA (titer 9 X 105 virions/ml) produces a greater than 90% reduction in the tumor size when cells are injected into an estrogen-dependent nude mouse model (compared with control MMTV-based viral vectors). Based upon these findings, we have proposed a clinical trial to determine if infusion of antisense c-fos viral vectors will induce regression of metastatic breast cancer in the peritoneum (malignant ascites) or pleura (malignant pleuritis). The patient population will consist of women who have failed standard therapy and have extensive, biopsy or cytology-proven metastatic breast cancer involving the peritoneum or pleura which result in malignant effusions. In this protocol, patient effusions will be drained daily for 4 days and the fluid replaced with retroviral vector. These are patients who have failed standard therapy for their cancer and are expected to survive for a few months.