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Table 1 Selected studies of intravenous oncolytic virus delivery

From: Two roads for oncolytic immunotherapy development

Study OV species Tumors targeted Sample size Dose range Treatment schedule Intratumoral OV analysis Adverse events
Machiels et al. [6] Adenovirus Epithelial adeno Carcinomas 61 1 × 1010–1 × 1013 vp Days 1, 3 and 5 weekly and every 3-week schedule One patient with colorectal cancer abdominal wall metastasis sample was + by IHC and qPCR 39 days after treatment Hypoxia, lymphopenia, neutropenia
Nemunaitis et al. [8] Adenovirus (ONYX-015) Solid tumors metastatic to lung 10 2 × 1010–2 × 1013 vp Weekly in 21 day cycle qPCR and IHC
Virus seen in one tumor biopsy
Flu-like symptoms, transient transaminitis
Hamid et al. [9] Adenovirus Metastatic colorectal cancer 18 2 × 1012 vp Every 2 weeks One autopsy patient with tumor at the root of the mesentery by PCR and IHC flu-like symptoms, chills, fatigue and lethargy
Rudin et al. [10] Seneca valley virus Small cell lung cancer and carcinoid tumors 30 107 – 1011 vp Single dose qPCR and IHC one autopsy-derived tumor had + IHC for virus Flu-like symptoms
Park et al. [11] Vaccinia virus-GM-CSF Treatment-refractory colorectal cancer 15 1 × 106 – 3 × 107 pfu Every 14 days Plaque assay on plasma and throat swabs Flu-like symptoms
Downs-Canner et al. [12] Vaccinia virus Advanced colorectal or other solid cancers 11 3 × 108–3 × 109 pfu Single dose qPCR
Plaque assay detected 2.5 × 103 pfu in one patient
fever, chills, abdominal pain, nausea, vomiting, fatigue
Garcia et al. [13] Adenovirus type 5 Metastatic melanoma 12 1 × 1013 vp Single infusion qPCR
Viral DNA was only detected in patients treated with doses > 3.3 × 1011
flu- like syndrome fever, chills, neutropenia
Garcia-Carbonero, et al. [7] Adenovirus Solid adenocarcinomas 17 12 by IV
5 by IT inj.
1 × 1012 vp Days 1, 3 and 5 followed by tumor resection Virus 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 specimens
None
Mell et al. [14] Vaccinia virus Head and neck cancer 19 3 × 108–3 × 109 pfu Day 3
Day 3 and 8
Days 3, 8, 15 and 22
Radiation 33–35 fractions
Cisplatin on days 1, 22 and 43
qPCR+ in 5 patients (range 4–409 copies/mg)
Virus (2.0 × 103 pfu) detected in tongue tumor in 1 patient at 7 days
Rigors, fever, fatigue, rash, hypotension, mucositis, nausea, vomiting
Samson et al. [15] Reovirus Brain tumors 9 1 × 1010 TCID50 Single one-hour infusion IHC for reovirus ó3 capsid protein was low in 6/9 tumors
igTEM + in 9/9
ISH+  8/9
qPCR+ in 4/7
Lymphopenia, flu-like symptoms
  1. 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