Table 1. Clinical trials with inactivated and oncolytic paramyxoviruses.
| Viral strain | Route of administration | Material, dosage, duration | Disease | Clinical study and patient number (n) | Clinical outcome | Year | References |
|---|---|---|---|---|---|---|---|
| Sendai virus | |||||||
| Sendai virus (UV inactivated VR105, i.e. Sendai/52) | Intratumoral | Viral particles, 6 times injection with 3,000 mNAU or 10,000 mNAU of inactivated SeV in 2 weeks/one cycle. Two cycles with 4-week interval | Advanced melanoma | Phase 1/2a (n = 6) | In progress | 2009 | Personal communication of Dr Kaneda |
| Sendai virus alive (Moscow strain) | Intradermal and/or intratumoral | Virus mixed with chicken embryo cells, 107–108 EID50 virus and 2 × 107 cells, every 7–10 days during 4 months | Advanced cancers without metastases debulking | Case series (n = 47) | 31 out of 47 patients responded to therapy, with six major responses (complete tumor regression followed by 5–7 years of disease-free survival) | 1995 | Personal communication of Dr V. Senin |
| The same as above plus allogenic or autologous cells (0.5–2 × 107 cells), every 7–10 days during 4 months | Advanced metastatic cancers after tumor debulking surgery | Case series (n = 15) | 4 out of 15 patients experienced remaining tumor shrinking and survived at least 1 year without disease progression | 1996 | |||
| Intradermal | Advanced metastatic cancers after radical cytoreductive surgery | Case series (n = 12) | 11 out of 12 patients experienced disease-free survival for at least 1 year | 1996 | |||
| Newcastle disease virus | |||||||
| Attenuated NDV | |||||||
| NDV-73 T mesogenic | Subcutaneous injection | Allogenic or autologous human melanoma cells infected with NDV, weekly injections | Melanoma (stage II) | Phase 2 (n = 83) | 10 years of survival was above 60% versus 6–33% of historic control, 15 years survival was 55% for NDV-treated patients | 1992 | 138,139 |
| NDV-MTH-68 mesogenic | Inhalation | 4 × 103 PFU (biweekly for 6 months) | Advanced cancers | Phase 2 (n = 33) | 1-year survival for 22 out of 33 versus 4 out of 26 in control group; 2-year survival for 7 out of 33 versus 9 out of 26 in control group | 1993 | 133 |
| NDV-MTH-68 mesogenic | i.v. and inhalation | 2 × 107 to 2.5 × 108 PFU (dosage step + maintenance dose) daily with alternate route of delivery | Glioblastoma multiforme | Case series (n = 14) | 7 out of 14 responses; four major, 5–9-year survival or more | 2004 | 134 |
| NDV-HUJ lentogenic | i.v. | Dose escalation up to 55 × 109 EID50 | Glioblastoma multiforme | Phase 1 (n = 11) | One patient out of 11 achieved a complete response, all others had progressive disease | 2006 | 135 |
| NDV-PV701 mesogenic | i.v. | Dose escalation up to 1.20 × 1011 PFU | Advanced cancers | Phase 1 (n = 79) | Objective responses occurred at higher dose levels. Four out of 79 responses: two major, two minor, progression-free survival ranged from 4 to 31 months | 2002 | 144 |
| NDV-PV701 mesogenic | i.v. | Dose escalation up to 1.20 × 1011 PFU | Advanced cancers | Phase 1 (n = 16) | One patient experienced near-complete response with at least 1-year survival, four others from the treatment group had disease stabilization | 2006 | 147 |
| 1.2 × 1011 PFU | Advanced cancers | Phase 1 (n = 18) | Six out of 18 responses: one complete, three partial, and two minor; six patients with 2-year survival or more | 2007 | 136,137 | ||
| NDV Ulster lentogenic | Intradermal injections | Allogenic or autologous tumor cells infected with NDV, biweekly injections,5 total plus | Glioblastoma multiforme | Phase 1/2 (n = 23) | One patient was long term survivor versus none in a control group of 87 patients | 2004 | 181 |
| Per vaccine, 1 × 107 tumor cells were incubated for 1 hour with 64 HA units of the NDV | |||||||
| Head and neck squamous cell carcinomas | Phase 2 (n = 20) | 5-year survival was 51% | 2005 | 140,141 | |||
| Advanced colorectal cancer after resection of liver metastases | Phase 3 (n = 50) (randomized) | Subgroup of colon cancer patients analysis revealed a significant advantage for vaccinated colon cancer patients with respect to overall survival (hazard ratio: 3.3; 95% confidence interval (CI): 1.0–10.4; P = 0.042) and metastases-free survival (hazard ratio: 2.7; 95% CI: 1.0–7.4; P = 0.047) | 2009 | 142 | |||
| Measles virus | |||||||
| Attenuated MV | |||||||
| MV-EZ | Intratumoral | 102–103 TCID50 | Subcutaneous T-cell lymphoma | Phase 1 (n = 5) | One out of five complete regression of injected lesion, three out of five partial regression of injected lesions and two of these patients also experienced partial regression of distant lesions | 2005 | 149 |
| MV-CEA | Intraperitoneal | 103–109 TCID50 (every 4 weeks for 6 months) | Ovarian cancer | Phase 1 (n = 21) | 14 out of 21 responses: mean 1-year survival; one patient with 3.2-year survival | 2010 | 150 |
| MV-CEA | Intratumoral/excised tumor cavity | Glioblastoma multiforme | Phase 1 | In progress | |||
| MV-NIS | Intravenous | Multiple myeloma | Phase 1 | In progress. After only one viral infusion, tumor-selective MV-NIS replication was observed that led to complete remission of a disseminated malignancy in one patient out of two infused. | 2014 | 151 | |
| MV-NIS | Intraperitoneal | 108–109 TCID50 (every 4 weeks for 6 months) | Ovarian cancer | Phase 1 | Median overall survival of 26.5 months | 2015 | 152 |
| Mumps virus | |||||||
| WT mumps virus | |||||||
| Urabe strain | Topically, intravenously, or by inhalation | 105–107 TCID50 | Advanced cancers | Phase 2 (n = 90) | 79 out of 90 patients responded to therapy and 37 out of 79 got significant or complete tumor regression | 1974 | 154 |
| Urabe strain | 108–109 PFU | Advanced cancers | Phase 2 (n = 200) | 26 out of 200 patients experienced tumor regression; majority of others experienced objective symptoms relief | 1978 | 155 | |
| Attenuated mumps virus | |||||||
| Attenuated Urabe strain | Subcutaneous presensitization intraperitoneal, intrathoracic and intratumoral | 108–109 PFU | Gynecologic cancers | Phase 2 (n = 22) | Five out of seven patients with malignant ascites or pleural effusions experienced complete disappearance of disease manifestation; however, patients with large tumor masses did not respond. A clinical response was obtained in patients with ascites or pleural fluid who had received viral preimmunization | 1988 | 153 |
CEA, carcinoembryonic antigen; EID50, 50% embryo infective dose; EZ, Edmonston–Zagreb; HUJ, Hebrew University in Jerusalem; MTH, mesogenic strain of Newcastle disease virus; MV, measles virus; NAU, neuraminidase unit; NDV, Newcastle disease virus; NIS, thyroidal sodium iodide symporter; PFU, plaque-forming units; TCID50, 50% tissue culture infectious dose; WT, wild-type.