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Mol Ther. 2015 Jan;23(1):202-14. doi: 10.1038/mt.2014.194. Epub 2014 Oct 8.

First-in-man study of western reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity.

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Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Department of Pathology, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
1] Department of Pharmacology, Pusan National University, Busan, South Korea [2] SillaJen, Inc., Seoul, South Korea.
SillaJen, Inc., Seoul, South Korea.


Oncolytic viral therapy utilizes a tumor-selective replicating virus which preferentially infects and destroys cancer cells and triggers antitumor immunity. The Western Reserve strain of vaccinia virus (VV) is the most virulent strain of VV in animal models and has been engineered for tumor selectivity through two targeted gene deletions (vvDD). We performed the first-in-human phase 1, intratumoral dose escalation clinical trial of vvDD in 16 patients with advanced solid tumors. In addition to safety, we evaluated signs of vvDD replication and spread to distant tumors, pharmacokinetics and pharmacodynamics, clinical and immune responses to vvDD. Dose escalation proceeded without dose-limiting toxicities to a maximum feasible dose of 3 × 10(9) pfu. vvDD replication in tumors was reproducible. vvDD genomes and/or infectious particles were recovered from injected (n = 5 patients) and noninjected (n = 2 patients) tumors. At the two highest doses, vvDD genomes were detected acutely in blood in all patients while delayed re-emergence of vvDD genomes in blood was detected in two patients. Fifteen of 16 patients exhibited late symptoms, consistent with ongoing vvDD replication. In summary, intratumoral injection of the oncolytic vaccinia vvDD was well-tolerated in patients and resulted in selective infection of injected and noninjected tumors and antitumor activity.

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