Selected studies of intravenous oncolytic virus delivery

StudyOV speciesTumors targetedSample sizeDose rangeTreatment scheduleIntratumoral OV analysisAdverse events
Machiels et al. [6]AdenovirusEpithelial adeno Carcinomas611 × 1010–1 × 1013 vpDays 1, 3 and 5 weekly and every 3-week scheduleOne patient with colorectal cancer abdominal wall metastasis sample was + by IHC and qPCR 39 days after treatmentHypoxia, lymphopenia, neutropenia
Nemunaitis et al. [8]Adenovirus (ONYX-015)Solid tumors metastatic to lung102 × 1010–2 × 1013 vpWeekly in 21 day cycleqPCR and IHCVirus seen in one tumor biopsyFlu-like symptoms, transient transaminitis
Hamid et al. [9]AdenovirusMetastatic colorectal cancer182 × 1012 vpEvery 2 weeksOne autopsy patient with tumor at the root of the mesentery by PCR and IHCflu-like symptoms, chills, fatigue and lethargy
Rudin et al. [10]Seneca valley virusSmall cell lung cancer and carcinoid tumors30107 – 1011 vpSingle doseqPCR and IHC one autopsy-derived tumor had + IHC for virusFlu-like symptoms
Park et al. [11]Vaccinia virus-GM-CSFTreatment-refractory colorectal cancer151 × 106 – 3 × 107 pfuEvery 14 daysPlaque assay on plasma and throat swabsFlu-like symptoms
Downs-Canner et al. [12]Vaccinia virusAdvanced colorectal or other solid cancers113 × 108–3 × 109 pfuSingle doseqPCRPlaque assay detected 2.5 × 103 pfu in one patientfever, chills, abdominal pain, nausea, vomiting, fatigue
Garcia et al. [13]Adenovirus type 5Metastatic melanoma121 × 1013 vpSingle infusionqPCRViral DNA was only detected in patients treated with doses > 3.3 × 1011flu- like syndrome fever, chills, neutropenia
Garcia-Carbonero, et al. [7]AdenovirusSolid adenocarcinomas17 12 by IV5 by IT inj.1 × 1012 vpDays 1, 3 and 5 followed by tumor resectionVirus hexon protein by IHC found in 10 patients> 80% nuclear staining seen in 21.1% of IT-inj. and 9.4% for IV-inj. Tumor specimensNone
Mell et al. [14]Vaccinia virusHead and neck cancer193 × 108–3 × 109 pfuDay 3Day 3 and 8Days 3, 8, 15 and 22Radiation 33–35 fractionsCisplatin on days 1, 22 and 43qPCR+ in 5 patients (range 4–409 copies/mg)Virus (2.0 × 103 pfu) detected in tongue tumor in 1 patient at 7 daysRigors, fever, fatigue, rash, hypotension, mucositis, nausea, vomiting
Samson et al. [15]ReovirusBrain tumors91 × 1010 TCID50Single one-hour infusionIHC for reovirus ó3 capsid protein was low in 6/9 tumorsigTEM + in 9/9ISH+  8/9qPCR+ in 4/7Lymphopenia, flu-like symptoms

Abbreviations: igTEM immunogold transmission electron microscopy, inj. injection, IT intratumoral, IV intravenous, pfu plaque-forming units, qPCR quantitative polymerase chain reaction assay, TCID tissue culture infective dose, vp viral particle