Copper chelation enhances antitumor efficacy and systemic delivery of oncolytic HSV.

ABSTRACT:

Purpose

Copper in serum supports angiogenesis and inhibits replication of wild-type HSV-1. Copper chelation is currently being investigated as an antiangiogenic and antineoplastic agent in patients diagnosed with cancer. Herpes simplex virus-derived oncolytic viruses (oHSV) are being evaluated for safety and efficacy in patients, but several host barriers limit their efficacy. Here, we tested whether copper inhibits oHSV infection and replication and whether copper chelation would augment therapeutic efficacy of oHSV.

Experimental design

Subcutaneous and intracranial tumor-bearing mice were treated with oHSV ± ATN-224 to evaluate tumor burden and survival. Virus replication and cell killing was measured in the presence or absence of the copper chelating agent ATN-224 and in

SUBMITTER: Yoo JY 

PROVIDER: S-EPMC3784008 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature