Ovarian cancer is one of the leading causes of death due to cancer in women and the most fatal gynecologic malignancy in the U.S. Over seventy percent of women affected by ovarian cancer will present with advanced stage disease at the time of initial diagnosis. The long-term survival for patients with advanced stage ovarian carcinoma has remained approximately 15-30% over the last 20 years. Clearly, more effective treatment strategies are needed for patients affected by this disease. To address this clinical need, our investigative team has developed an infectivity enhanced conditionally enhanced replicative adenovirus (CRAd) that is now poised to be investigated in a clinical trial context in patients with recurrent ovarian cancer. This CRAd, Ad5-?24RGD, has been demonstrated to more efficiently transfect and replicate in established and primary ovarian cancer cell lines, to achieve (by virtue of its efficient replication) potent ovarian cancer cell death, to enhance survival in an ovarian cancer animal model, and to be associated with an acceptable safety profile in preclinical safety studies. Our hypothesis is that an intraperitoneally (IP) administered infectivity enhanced CRAd is both safe and potentially efficacious in patients with recurrent ovarian cancer. Thus, our specific aims are 1) To determine the maximum tolerated dose, spectrum of toxicities, and potential antitumor clinical activity encountered with IP delivery of a RGD modified CRAd (Ad5-?24RGD) in patients with recurrent ovarian cancer; 2) To determine the biologic effects encountered with IP delivery of Ad5-?24RGD in patients with recurrent ovarian cancer; 3) To determine the immunologic response generated against Ad5-?24RGD when administered IP to patients with recurrent ovarian cancer. Knowledge gained by these studies could lead to improved therapy for ovarian and other cancer patients and lead to important advancements in the field of gene therapy in general. Clearly, more effective treatment strategies are needed for patients affected by ovarian cancer, which is one of the leading causes of death due to cancer in women and the most fatal gynecologic malignancy in the U.S. To address this clinical need, our investigative team has developed an infectivity enhanced conditionally enhanced replicative adenovirus (CRAd) that is now poised to be investigated in a clinical trial context in patients with recurrent ovarian cancer. Knowledge gained by these studies could lead to improved therapy for ovarian and other cancer patients and lead to important advancements in the field of gene therapy in general. ? ? ?
| Kimball, Kristopher J; Preuss, Meredith A; Barnes, Mack N et al. (2010) A phase I study of a tropism-modified conditionally replicative adenovirus for recurrent malignant gynecologic diseases. Clin Cancer Res 16:5277-87 |
