Sensitivity of Breast Tumors to Oncolytic Viruses
Annual rept. 15 Jul 2004-14 Jul 2005
WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
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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 antitumor 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-M virus to selectively target and kill tumor cells, we carried out a combination treatment together with the anti-tumor cytokine, IL-12. Our results indicated that the combination therapy was more effective than individual therapies at preventing the growth of the tumor. Therefore, using a virus that induces the immune response, together with an anti-tumor cytokine, IL-12, enhances the killing potential in an aggressive breast tumor model. The information obtained from these studies will allow us to develop better viral or combination therapies to treat aggressive tumors that are resistant to more conventional therapies.
- Medicine and Medical Research