Treating tumors with a vaccinia virus expressing IFNΒ Illustrates the complex relationships between oncolytic ability and immunogenicity

Liang Chuan S. Wang, Rachel C. Lynn, Guanjun Cheng, Edward Alexander, Veena Kapoor, Edmund K. Moon, Jing Sun, Zvi G. Fridlender, Stuart N. Isaacs, Stephen H. Thorne, Steven M. Albelda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Since previous work using a nonreplicating adenovirus-expressing mouse interferon-Β (Ad.mIFNΒ) showed promising preclinical activity, we postulated that a vector-expressing IFNΒ at high levels that could also replicate would be even more beneficial. Accordingly a replication competent, recombinant vaccinia viral vector-expressing mIFNΒ (VV.mIFNΒ) was tested. VV.mIFNΒ-induced antitumor responses in two syngeneic mouse flank models of lung cancer. Although VV.mIFNΒ 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.mIFNΒ 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.

Original languageAmerican English
Pages (from-to)736-748
Number of pages13
JournalMolecular Therapy
Issue number4
StatePublished - Apr 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NCI (National Cancer Institute) grant P01 CA66726 (to S.M.A.), and an NRSA (National Research Service Award) training grant 5-T32 HL07748 (to L.-C.S.W.). S.N.I. was supported by U01 AI066333, and S.H.T. was supported by NCI grant R01 CA140215. The authors thank Jennerex Biotherapeutics for providing the vaccinia viral vectors. The authors declared no conflict of interest.


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