Complement inhibition prevents oncolytic vaccinia virus neutralization in immune humans and cynomolgus macaques.

ABSTRACT: Oncolytic viruses (OVs) have shown promising clinical activity when administered by direct intratumoral injection. However, natural barriers in the blood, including antibodies and complement, are likely to limit the ability to repeatedly administer OVs by the intravenous route. We demonstrate here that for a prototype of the clinical vaccinia virus based product Pexa-Vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune virus treated cancer patients, is strictly dependent on the activation of complement. In immunized rats, complement depletion stabilized vaccinia virus in the blood and led to improved delivery to tumors. Complement depletion also enhanced tumor infection when virus was directly injected into tumors

SUBMITTER: Evgin L 

PROVIDER: S-EPMC4817751 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature