Year: 2017
Type: dissertation
Abstract: Many oncolytic viruses (OVs), such as double-deleted vaccina virus (vvDD), are engineered with enhanced tumor-selectivity based on increased cell proliferation in cancer cells. We proposed that OVs with improved tumor efficacy and equal tumor-selectivity could be generated by exploiting the dysregulated immune response in tumors. Vaccinia virus (VV) proteins that inhibit the interferon response are redundant for replication in tumors, which often already have a decreased interferon response. We deleted VV immunomodulatory genes (N1L, K1L, K3L, A46R, or A52R) from VV and compared these candidate VVs to vvDD. Candidate VVs demonstrated equal or superior in vitro viral replication, spread, and tumor cytotoxicity in colon cancer cells compared to vvDD and were potent against ovarian cancer cells. At doses 20-1000 times less than the vvDD treatment dose, the best in vitro candidate VVs (â K1L, â A46R, â A52R VVs) demonstrated tumor-selectivity and equal or prolonged survival in mouse models of peritoneal carcinomatosis.
Source: TSpace (University of Toronto)
Author: Tiffany Ho
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2778918237