Table 1.

Oncolytic virus candidates for glioma therapy with summary of tumor selectivity factors

Virus	Gemone and structure	Host and virus family	Determinants for tumor selective targeting or replication	Phase of development relating to glioma
HSV1	ds DNA Enveloped	Human Herpesviridae	1) HSV-TK and RR mutations compensated by activated cell cycle in tumors 2) PKR defects in tumors allow γ134.5 deleted HSV to replicate 3) ICP47 gene deletion acts immune -stimulatory	Clinical phase I/II
NDV	ss (−) RNA Enveloped	Avian Paramyxoviridae	1) Mainly induction of antitumor cytokines and immune response 2) Possibly exploiting IFN defects	Clinical phase I/II
Adeno	ds DNA Naked	Human Adenoviridae	1) Defects in p53 or RB pathway targeted by E1B and E1A mutants 2) RGD modification targets tumor integrins 3) E2F1 responsive elements control viral replication	Clinical phase I
Reo	ds RNA Naked	Mammalian Reoviridae	1) Tropism for Ras – activated, transformed tumor cells	Clinical phase I
Vaccinia	ds DNA Enveloped	Cow/Horse (?) Poxviridae	1) TK deletion compensated by nucleotide abundance in transformed tumors 2) VGF deletions compensated by aberrant EGFR receptor activation 3) Large size requires leaky tumor vessels for viral extravasation	Preclinical in vivo
Polio	ss (+) RNA Naked	Human Picornaviridae	1) Polio receptor CD46 expressed on glioma 2) Pathogenic polio IRES replaced with rhinovirus IRES	Clinical phase I
VSV	ss (−) RNA Enveloped	Livestock Mosquito Rhabdoviridae	1) Selective replication depends on defective IFN pathway in tumor cells	Preclinical in vivo
MVM	ss DNA Naked	Mouse Parvoviridae	1) Actively dividing cells required for replication 2) Defects in PKR augment viral replication	Preclinical in vitro
Sindbis	ss (+) RNA Enveloped	Mammalian/ Mosquito Togaviridae	1) Sindbis binds to 67kDa Laminin receptor, which is overexpressed on some tumors	Preclinical in vitro
PRV	ds DNA Enveloped	Pig Herpesviridae	1) HSV-TK and RR mutations compensated by activated cell cycle in tumors	Preclinical in vitro
Measles	ss (−) RNA Enveloped	Human Paramyxoviridae	1) Binding to CD-46 receptor, overexpressed on tumors	Clinical phase I
Myxoma	ds DNA Enveloped	Rabbit Poxviridae	1) Replication in IFN deficient tumor cells 2) High affinity to cells with activated Akt	Preclinical in vivo
H1PV	ss DNA Naked	Rat Parvoviridae	1) Virus requires actively dividing cells in S-phase for replication 2) Defects in PKR augment viral replication	Clinical phase I
SVV	ss (+) RNA Naked	Pig Picornaviridae	1) Strong tropism to neuroendocrine and solid pediatric tumors, possibly mediated through integrin α4 receptor binding	Preclinical in vitro

Abbreviations: HSV1, herpes simplex virus 1; NDV, Newcastle disease virus; VSV, vesicular stomatitis virus; MVM, minute virus of mice; PRV, pseudorabies virus; H1PV, rat parvovirus H1; SVV, Seneca Valley virus; ds, double-stranded; ss, single-stranded; TK, thymidine kinase; RR, ribonucleotide reductase; PKR, protein kinase R; IFN, interferon; RB, retinoblastoma tumor suppressor; VGF, VGF nerve growth factor inducible; EGFR, epidermal growth factor receptor; IRES, internal ribosomal entry site.