abstract |
The present invention relates to replication-competent adenovirus vectors which are specific for cells which allow an osteocalcin transcriptional regulatory sequence to function, such as prostate cancer cells, prostate stromal cells, vascular pericytes, proliferating cancer-associated osteoblasts, and prostate cancer and associated bone stromal cells which fail to express PSA or androgen receptor (AR), and methods of use of such viruses are provided. These viruses comprise an adenoviral gene under control of an osteocalcin transcriptional regulatory sequence. The gene can be, for example, a gene required for adenoviral replication. The viruses can also comprise at least one additional adenoviral gene under control of at least one additional tissue-specific transcriptional regulatory sequence. Thus, virus replication can be restricted to target cells exhibiting osteocalcin gene expression. Such replication-competent adenovirus vectors are useful in the treatment of prostate cancer, brain cancer, ovarian cancer, thyroid cancer, tumors, osteosarcoma, occular melanoma, lung cancer, or breast cancer. |