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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.

Author information

1
Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.
2
Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital Research Institute, Columbus, Ohio.
3
Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
4
Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio.
5
Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
6
Translational Research Trials Office, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
7
Virttu Biologics Ltd, Biocity, Scotland, United Kingdom.
8
Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio. Timothy.Cripe@nationwidechildrens.org.

Abstract

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.

PMID:
28495911
DOI:
10.1158/1078-0432.CCR-16-2900
[Indexed for MEDLINE]
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