Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients.
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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DOI：
10.1158/1078-0432.ccr-16-2900
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发表时间：
2017-07-15
影响因子：
11.5
通讯作者：
Cripe, Timothy P.
中科院分区：
文献类型：
--
作者：
Streby, Keri A.;Geller, James I.;Currier, Mark A.;Warren, Patrick S.;Racadio, John M.;Towbin, Alexander J.;Vaughan, Michele R.;Triplet, Melinda;Ott-Napier, Kristy;Dishman, Devon J.;Backus, Lori R.;Stockman, Beth;Brunner, Marianne;Simpson, Kathleen;Spavin, Robert;Conner, Joe;Cripe, Timothy P.
HSV1716 is an oncolytic herpes simplex virus-1 studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric cancer patients, we conducted a phase 1 trial of image-guided injection in young patients with relapsed or refractory extracranial cancers. We delivered a single dose of 105–107 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 polymerase chain reaction and culture. 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 polymerase chain reaction 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 positron emission tomography, 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. 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.
