IL-12-mediated toxicity from localized oncolytic virotherapy can be reduced using systemic TNF blockade.

ABSTRACT: Cytokine therapy represents an attractive option to improve the outcomes of cancer patients. However, the systemic delivery of these agents often leads to severe immune-related toxicities, which can prevent their efficient clinical use. One approach to address this issue is the use of recombinant oncolytic viruses to deliver various cytokines directly to the tumor. This improves the biodistribution of the secreted cytokine-transgenes, both augmenting antitumor immune responses and decreasing systemic toxicities. We have shown recently that a doubly recombinant oncolytic myxoma virus that secretes a soluble version of PD1 as well as an interleukin-12 (IL-12) fusion protein (vPD1/IL-12) can cause potent regression of disseminated cancers. Here we show that, despite the predominant localizati

SUBMITTER: Valenzuela-Cardenas M 

PROVIDER: S-EPMC11407086 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature