AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer
Abstract
To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. To test this protein therapeutic, malignant ascites from patients with highly resistant recurrent ovarian cancer were used to create patient-derived ovarian cancer xenografts. Mice bearing tumors were treated with adeno-associated virus serotype 9 gene therapy delivering MIS, which inhibited three of five models without signs of toxicity. Finally, we found that 88% of serous tumors express MIS type II receptor by immunohistochemistry. These preclinical data suggest that gene therapy with MIS provides a potentially well-tolerated and effective treatment strategy for chemoresistant serous ovarian cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 27, 2015
- Source ID
- 10.1073/pnas.1510604112
Entities
People
- Aaron Yu
- Amanda Sosulski
- Caroline M. Coletti
- Cesar M Castro
- Dan Wang
- David Pépin
- Guangping Gao
- Katherine Hendren
- Lihua Zhang
- Michael J. Birrer
- Patricia K. Donahoe
- Vinod Vathipadiekal
Organizations
- Harvard Medical School
- United States Department of Defense
- University of Massachusetts Medical School