Oncolytic herpes simplex viruses (oHSV), which kill tumor cells, have shown promise in the treatment of patients with recurrent brain tumors. BTP members study improvements to effective therapy, which include overcoming limited vector distribution on delivery, a consequence of injected virus getting trapped in the tumor extracellular matrix (ECM). These virus vectors are also used as a strategy for multi-gene delivery for combinatorial therapy.
- Glioma cells which secrete chondroitin sulfate proteoglycans possibly inhibit oncolytic viral (OV) therapy. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove chondroitin sulfate glycosaminoglycans from proteoglycans without any deleterious effects in vivo. Degradation of glioma extracellular matrix with OV-expressing bacterial Chase-ABC enhanced OV spread and antitumor efficacy (Dmitrieva et.al., Clin Cancer Res. 2011, 17:1362-72).
- MMP-9 expression improved the distribution and infection of oHSV vectors in spheroid model in vitro. Furthermore, MMP9 induced a vector infection over larger areas of brain tumors in vivo. These results suggest that vector delivery and distribution in vivo can be improved by compromising the ECM, potentially enhancing oncolytic efficacy (Hong et.al., Gene Ther. 2010, 17:1200-5).
|Glorioso, Joseph, PhD
Microbiology and Molecular Genetics
|Niranjan, Ajay, MD
|Grandi, Paola, PhD