Treating tumors with a vaccinia virus expressing IFN? illustrates the complex relationships between oncolytic ability and immunogenicity.

ABSTRACT: Since previous work using a nonreplicating adenovirus-expressing mouse interferon-? (Ad.mIFN?) showed promising preclinical activity, we postulated that a vector-expressing IFN? at high levels that could also replicate would be even more beneficial. Accordingly a replication competent, recombinant vaccinia viral vector-expressing mIFN? (VV.mIFN?) was tested. VV.mIFN?-induced antitumor responses in two syngeneic mouse flank models of lung cancer. Although VV.mIFN? had equivalent in vivo efficacy in both murine tumor models, the mechanisms of tumor killing were completely different. In LKRM2 tumors, viral replication was minimal and the tumor killing mechanism was due to activation of immune responses through induction of a local inflammatory response and production of antitumor CD8 T-cells. In contrast, in TC-1 tumors, the vector replicated well, induced an innate immune response, but antitumor activity was primarily due to a direct oncolytic effect. However, the VV.mIFN? vector was able to augment the efficacy of an antitumor vaccine in the TC-1 tumor model in association with increased numbers of infiltrating CD8 T-cells. These data show the complex relationships between oncolytic viruses and the immune system which, if understood and harnessed correctly, could potentially be used to enhance the efficacy of immunotherapy.

SUBMITTER: Wang LC 

PROVIDER: S-EPMC3321606 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature