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Clin Cancer Res. 2017 Jul 15;23(14):3566-3574. doi: 10.1158/1078-0432.CCR-16-2900. Epub 2017 May 11.

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients.

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Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital Research Institute, Columbus, Ohio.
Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio.
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Translational Research Trials Office, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Virttu Biologics Ltd, Biocity, Scotland, United Kingdom.
Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.


Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.Experimental Design: We delivered a single dose of 105 to 107 infectious units of HSV1716 via computed tomography-guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on 18fluorine-deoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 23(14); 3566-74. ©2017 AACR.

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