Table 2.

Preclinical studies of RNA viruses in glioma tumors.

Virus	Modifications	Cell Lines	In Vivo Models	Results
Reovirus	Reovirus	Human: 24 GBM cell lines [99]	U87 and U251 intracranial and subcutaneous in SCID mice	Death in 20 out of 24 GBM lines Regression in both in vivo models Toxicity in nude mice.
		Human: U87 and 2 patient-derived lines [100]	GL261 intracranial in C57/BL6	i.v. administration reaches brain tumors. T cell tumor recruitment and cytotoxicity. Synergy with anti PD-L1.
Measles	MV-CEA: CEA expression.	Human: U87, U251, and U118 [105]	U87 intracranial and subcutaneous in nude mice	Regression in s.c. tumor after intravenous and intratumor administration. Regression in intracranial tumor after intratumor administration.
	MV-NIS: NIS expression.	Human: U87, U251 and 6 patient derived GBM [106]	U251 subcutaneous and GBM intracranial in nude mice	Synergic effect of virotherapy and radiotherapy.
	MV-GFP-HAA-scEGFR: H protein partial deletion. scEGFR insertion in H protein.	Human: 5 patient derived GBM [107]	GBM intracranial in nude mice Mouse model Ifnarko CD46 Ge	Tumor regression after intratumor administration. No toxicity in CNS.
	MV-141.4: scFvCD133 insertion in H.	Human: primary GBM [111]	GBM intracranial in NOD/SCID	Better survival rate in comparison with MV-Edm.
VSV	VSV WT	-	C6 subcutaneous nude mice [112]	Inhibition of tumor growth.
	VSV-ΔG: G protein deletion.	Human: U87 Rat: C6 [111]	-	Infection of cell lines. Rapid lysis.
	VSVΔM51: M51 single nucleotide deletion.	Human: 14 glioma cell lines and 15 primary gliomas [115]	U87 and U118 subcutaneous in nude mice	Infection and elimination of all cell lines. Tumor regression and prolonged survival.
	VSV-rp30: unknown viral glioma adaptation	Human: U87, U118, U373 and A172 [92]	U87 subcutaneous in nude mice	Increased selectivity and lytic capacity in glioblastoma cells. Tumor selectivity and cytopathic effect.
		Human: U87 and U118 [116]	U87 orthotopic in nude mice	Infection and lysis of brain and peripheral tumors.
	VSV-CT1/CT2: G protein partial deletion	Human: U87, U118, U373 and A172 [114]	U87 orthotopic in nude mice	Elimination of tumor cells. Normal cell toxicity can be eliminated with IFN co-treatment VSV-1p-GFP: infection and potent apoptosis over tumor.
	VSV-1p-GFP: GFP at the first position in the genome. VSV-CT9-M51: G protein partial deletion. M51 single nucleotide deletion.	Human: U87, U118, U373 and A172 Rat: 9L [119]	U87 orthotopic in CB17-SCID mice	VSV-CT1 and VSV-CT9-M51 have less toxicity than wt VSV. VSV-CT9-M51 is able to infect and kill tumors in brain.
	VSV-CT9-M51: G protein partial deletion. M51 single nucleotide deletion.	Human: primary GBM [122]	Orthotopic CB17 SCID	Coinfection with AAV-mIFN-β or with ribavirin enhances oncolytic properties.
Seneca Valley	SVV-001 WT	Human: primary GBM [138]	4 orthotopic models in nude mice	Partial response against glioma cells Effectivity in 2 of 4 in vivo tumors
		Human: GBM CSCs [139]	6 GBM CSC orthotopic nude mice	4 of 6 prolonged survival, tumor infection and cell lysis. Susceptibility dependent of sialic acid presence.
NDV	NDV WT	Human: 6 GBM CSCs [129]	Orthotopic nude mice	NDV replication is dependent on IFN deletion.
		Human: U87 and DBTRG.05MG [130]	Subcutaneous nude mice	Induce apoptosis. Decrease tumor volume.
		Human: A172 and U87 and 2 CSCs [131]	-	Induce apoptosis.
		Murine: GL261 [132]	GL261 orthotopic mice	NDV induces ICD.
		Human: T98G, LN18, U251, U87. Rat: C6 [133]	C6 in rats	Synergistic effects with TMZ. Decrease tumor volumes and increase OS.
Poliovirus	PVS-RIPO: IRES replaced with HRV2	Human: U87 [142]	-	Reduce viability.
		Human: CSCs and established cell lines [145]	HTB14 orthotopic and HTB15 flanks	Tumor regression.
		Human: 6 CSCs [143]	-	Cytolysis.
		Human: U87, HTB14 and HTB15 [144]	HTB15 in athymic Balb/c mice	Tumor regression.
Sindbis	Sindbis WT	Human: U87, U-118, U373, M059J, A172 [92]	U87 in flanks CB17-SCID mice	Effective replication and selective kill U87.
	Sindbis Gal.fu	Human: U87 [150]	U87 orthotopic in nude mice	Cytopathic activity.
RVFV	RVFV MP-12 and ZH548: attenuated strains	Rat: C6 [154] Human: U87 [155]	-	Infection occurs.

CEA: carcinoembryonic antigen; CNS: central nervous system; VSV: vesicular stomatitis virus; RVFV: RIFT valley fever virus; ICD: immunogenic cell death; OS: overall survival; PVS-RIPO: oncolytic polio/rhinovirus recombinant; IRES: internal ribosome entry site; HRV2: human rhinovirus 2.