. 2021 Jul 2;13(7):1294. doi: 10.3390/v13071294

Table 1.

Oncolytic viruses in clinical trials for treatment of malignant glioma.

Virus		Modification	Phase	Status	Reference	Route of Delivery	Results
HSV-1	G207	Deletions at both γ₁34.5 and ICP6 genes	I & II	Completed	NCT00028158 [53]	i.t./tumor resection cavity	No toxicity or serious adverse events.
			Ib	Completed	[52]	i.t.	No neurological adverse events after multiple virus dosages.
			I	Active, not recruiting	NCT02457845	i.t.
			II	Not yet recruiting	NCT04482933	i.t.
	G47Δ	G207 with triple mutations	I-IIa	Completed	UMIN000002661 (Japan)	i.t.	No toxicity or serious adverse events.
	G47Δ	G207 with triple mutations	II	Ongoing	UMIN000015995 (Japan)	i.t.	No toxicity with 1-year survival rate of 92.3% in 13 patients.
	rQNestin34.5v.2	Glioma-selective transcriptional regulator for expression of ICP34.5	I	Recruiting	NCT03152318	i.t.
HSV-1	M032	Deletions at both γ34.5; expression of human IL-12	I	Recruiting	NCT02062827	i.t.
	C134	Deletions at both γ34.5; Expression of HMCV IRS1 gene	I	Active, not recruiting	NCT03657576	i.t.
	HSV-1716	Deletion of both copies of RL1-gene-encoding ICP34.5 protein	I	Completed	[58]	i.t.	No adverse effects with 4 out of 9 patients surviving 14–24 months after virotherapy.
			I	Completed	[59]	Tumor resection cavity	No toxicity with 3 out of 12 patients surviving over a year.
			I	Terminated	NCT02031965	i.t.	NA
Adeno-virus	DNX-2401	Deletion of 24 base pairs from E1A; expression of RGD peptide motif	I	Completed	NCT00805376 [22]	i.t.	No dose-limiting virus toxicities reported with enhanced long-term survival and T cell response to tumors.
Adeno-virus	DNX-2401		I	Active, not recruiting	NCT03178032	Tumor resection cavity
Adeno-virus	DNX-2401	Deletion of 24 base pairs from E1A; Expression of arginine-glycine-aspartate peptide motif BM-hMSCs loaded with the DNX-2401DNX-2401 + Pembrolizumab	I	Completed	NCT01582516	i.t.	NA
			I	Completed	NCT01956734	i.t.	NA
			I	Completed	NCT02197169	i.t.	NA
			I	Recruiting	NCT03896568	i.a.
			II	Active, not recruiting	NCT02798406	i.t.
	DNX-2440	DNX-2401 expressing OX40L	I	Recruiting	NCT03714334	i.t.
	NSC-CRAd-Survivin-pk7	E1A expression under the control of human Survivin promoter; NSCs loaded with CRAd-survivin-pk7	I	Active, not recruiting	NCT03072134	i.t.
	ONYX-015	E1B-attenuated adenovirus	I	Completed	[60]	Tumor resection cavity	No serious adverse effects with 10¹⁰ pfu of virus; among 24 patients, 1 patient each showed no progression and regression.
Vaccinia	TG6002	Deletions of TK and 14L; expression of transgene FCU1	I/II	Recruiting	NCT03294486	i.v.
Reovirus	Reolysin	None	I	Completed	NCT00528684	i.t.	No dose-limiting toxicity even with the highest does of 1X10¹⁰ TCID₅₀.
			I	Completed	[61]	i.t.	No high-grade adverse effects. One and 10 out of 12 patients had a stable and progressive disease, respectively.
			Ib	Completed	[62]	i.v.	Reovirus is capable of infecting glioma tumors when injected i.v. and increases cytotoxic T cell infiltration in tumors.
		Reovirus + Sargramostim	I	Active, not recruiting	NCT02444546	i.v.
Parvovirus H-1	H-1PV		I/II	Completed	NCT01301430 [63]	i.v. or i.t. + tumor resection cavity	Virus was safe and well-tolerated. Induced cytotoxic T cell response.
Parvovirus H-1	H-1PV		I/IIa	Completed	[64]	i.t./i.v.	Enhanced immune response and improved median survival.
Poliovirus	PVSRIPO	Poliovirus IRES switched with HRV2 IRES	I	Recruiting	NCT03043391	i.t.
			I	Active, not recruiting	NCT01491893	i.t.	Improved survival rate with no neurovirulence.
			II	Active, not recruiting	NCT02986178	i.t.
Measles Virus	MV-CEA	Measles virus expressing CEA	I	Completed	NCT00390299	Tumor resection cavity	NA
Retroviral vector	Toca511	Replicating retroviral vector expressing cytosine deaminase	I	Completed	NCT01470794	Tumor resection cavity	Durable response rate in subgroup of malignant glioma patients.
			I	Completed	NCT01156584	i.t/i.v.	NA
			II & III	Terminated	NCT02414165	Tumor resection cavity	Failed to improve survival and meet other efficacy endpoints.
Newcastle disease virus	NDV-HUJ strain	Mutation at F1-F2 junction	I/II	Completed	[65]	i.v.	No severe toxicity with complete remission in 1 patient.
Newcastle disease virus	MTH-68/H		I	Completed	[66]	i.v.	No adverse effects with improved survival of 4–9 years in 4 patients.

Abbreviations: IL-12, interleukin-12; HMCV, human cytomegalovirus; HRV2, human rhinovirus type 2; IRES, internal ribosome entry site.; CEA, carcinoembryonic antigen; i.t., intratumoral; i.v., intravenous; i.t.; NA, not available.