Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus

Vaccinia virus (VV) is a powerful tool for cancer treatment with the potential tumor tropism, efficient cell-to-cell spread, rapid replication in cells, and stimulation of anti-tumor immunity. It has well-defined safety profile being assessed late-stage clinical trials. However, VV utility limited by bloodstream neutralization poor penetration into tumors. These factors have often restricted its route delivery to intratumoral or intrahepatic artery injection may impede repeat dosing. Chemical stealthing improves pharmacokinetics non-enveloped viruses, but it not yet been applied enveloped viruses such as VV. In present study, amphiphilic polymer was used coat VV, leading reduced binding neutralizing anti-VV antibody (81.8% polymer-coated [PCVV] staining positive versus 97.1% [p = 0.0038]). Attachment anti-mucin-1 (aMUC1) targeting antibody, give aMUC1-PCVV, enabled construct MUC1. high MUC1 expressing CAPAN-2 infection PCVV compared while restored aMUC1-PCVV. Pharmacokinetics PCVV, were evaluated. After intravenous (i.v.) 1 × 108 viral genomes (VG) 5 VG, circulation time aMUC1-PCVV increased, ~5-fold higher circulating dose at min