Sensitivity of Breast Tumors to Oncolytic Viruses
Abstract
The goal of this project is to develop novel therapies for breast cancer based on the oncolytic virus vesicular stomatitis virus (VSV). Studies have shown that matrix (M) protein mutants of VSV such as rM51R-M virus are excellent candidates for anti-tumor therapies due to the ability of these viruses to target and kill tumor cells while sparing normal cells. However not all tumors are amenable to VSV treatments in vivo. In data presented here we determined that normal mammary cells are more resistant to VSV-induced cytopathic effect than breast cancer cells. However in syngeneic breast cancer system in vivo rM51R-M virus is only partially effective at killing breast tumors derived from 4T1 cells. Our results indicate that the immune response may be attenuating the replication and spread of this virus at the tumor site. To enhance the ability of rM51R R-M virus to selectively target and kill tumor cells we carried out a combination treatment together with the anti-tumor cytokine lL-12. Our data indicate that rM51R R-M virus alone was as effective as lL-12 and the combination therapy at inducing an immune response during tumor therapies. Furthermore the combination therapy was as effective as single treatments at partially controlling the growth of the primary tumor. However it appeared to be slightly more effective at treating metastatic tumors. In conclusion although enhancing the immune response delays tumor growth none of these therapies were able to completely eliminate the existing tumor. It is possible that further enhancing the immune system may be helpful in overcoming suppressive tumor mechanisms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA462069
Entities
People
- Maryam Ahmed
Organizations
- Wake Forest University