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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