Table 1.
Viruses planned for or implemented in cancer gene therapy
| Genome | Family | Genus | Species/Strain/Vector |
|---|---|---|---|
| DNA | |||
| ds | Adenoviridae | Mastadenovirus | Ad serotype 5 and several derivatives in experimental settings [32], [59], [93], [94], [95], [96], [97], [102], [104], [110], [288] and in clinical trials [100], [289]. Conditionally replicating vectors based on canine adenovirus [111] |
| Aviadenovirus | Replication-deficient vector CELO [116] | ||
| Atadenovirus | The ovine adenovirus type 7 vectors OAdV623 and OAdV220 [114], [115] | ||
| Asfarviridae | n.f. | ||
| Herpesviridae | Simplexvirus | Several replication-competent vectors based on both natural and laboratory strains of human HSV-1 in experimental cancer targeting [60], [121], [124], [213] and in clinical trials [117], [119], [120]. Replication-competent vectors based on HSV-2 [88] | |
| Rhadinovirus | Replication-competent vectors based on bovine herpesvirus 4 [126] and saimiri virus [127], [128] | ||
| Varicellovirus | Replication-competent pseudorabies vectors [129] | ||
| Iridoviridae | n.f. | ||
| Papillomaviridae | n.f. | ||
| Polyomaviridae | Polyomavirus | Replication-deficient SV40 vector [85] | |
| Poxviridae | Orthopoxvirus | Replication-competent vectors based on vaccinia strains WR and Wyeth [132], [133], [134] | |
| Leporipoxvirus | Replication-competent vectors based on myxomavirus [139] | ||
| Yatapoxvirus | Replication-competent vectors based on yaba-like disease virus [138] | ||
| ds/ss | Hepadnaviridae | n.f. | |
| ss | Circoviridae | n.f. | |
| Parvoviridae | Parvovirus | Live autonomous rodent parvovirus H-1 [145]. Both live virus and replicons of minute virus of mice [131], [146]. Replicons of retargeted feline panleukopenia virus [147] | |
| Dependovirus | Replication-defective vectors based on several serotypes of adeno-associated virus [142], [143], [144] | ||
| RNA | |||
| ds | Birnaviridae | n.f. | |
| Reoviridae | Orthoreovirus | Live reovirus type 3 strain Dearing (T3D) in both pre-clinical experiments and in clinical trials [148], [149], [150] | |
| ss | − Arenaviridae | –⁎ | |
| Bornaviridae | n.f. | ||
| Bunyaviridae | –⁎ | ||
| Filoviridae | n.f. | ||
| Orthomyxoviridae | Influenza virus A | Replication-competent NS1 deleted influenza virus A [155] | |
| Paramyxoviridae | Avulavirus | Experimental therapy in several cancer models using live attenuated Newcastle disease virus strains such as 73-T, Ulster and Italien [69], [160]. Clinical trials with the live attenuated PV701 and MTH-68/H strains of Newcastle disease virus [2], [157], [159] | |
| Morbillivirus | Experimental cancer targeting with replication-competent vectors based on several measles virus strains, such as Jeryl Lynn, Moraten and Edmonston [46], [167], [168] Replication-competent measles vectors in clinical trials [169] | ||
| Respirovirus | Replication-deficient vector based on Sendai virus [63] | ||
| Rubulavirus | Live mumps virus in experimental settings [163] and in a clinical trial to treat ovarian cancer [290]. Non-oncolytic replication-competent vectors based on simian virus 5[164] | ||
| Rhabdoviridae | Vesiculovirus | Live attenuated vesicular stomatitis virus and recombinant derivatives [51], [52], [170], [171], [172], [174], [175], [176], [210] | |
| ss | + Arteriviridae | n.f. | |
| Astroviridae | n.f. | ||
| Caliciviridae | n.f. | ||
| Coronaviridae | Coronavirus | In vitro oncolytic activity of retargeted replication-competent vectors based on feline coronavirus and murine hepatitis virus [177], [178]. | |
| Flaviviridae | –⁎ | ||
| Nodaviridae | n.f. | ||
| Picornaviridae | Enterovirus | Live echovirus type 1 [40]. Live coxsackievirus A21 in experimental settings [38], [39] and in clinical trials [182]. Both a replicon vector [41] and replication-competent vectors of poliovirus type 1 [42], [179], also in a clinical trial (www.wiley.co.uk/genetherapy/clinical/). Live attenuated poliovirus [180] and bovine enterovirus [8], [183] in pre-clinical testing | |
| Unassigned | Live Seneca Valley virus SVV-001 in a clinical trial (www.neotropix.com) | ||
| Togaviridae | Alphavirus | Sindbis virus replicons [43], [186], [187] and live attenuated Sindbis virus [131], [188]. Replicons based on WT Semliki Forest virus [61], [189] and a replication-competent vector based on attenuated SFV [45] | |
| Retroviridae | Gammaretrovirus | Both replication-deficient and replication-competent MoMLV vectors [190], [191], [268], also used clinical trials [192], [193], [194] | |
| Lentivirus | Replication-deficient vectors based on HIV-1 [195], [276] | ||
| Spumavirus | Replication-competent vectors based on foamy virus [196] | ||
Listed are the virus families with a general vertebrate host range according to the 8th report of the International Committee on Taxonomy of Viruses (www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm) and those virus species, strains or vectors which currently are used or show promise of becoming tools for virotherapy. Although the list is by no means absolute it provides a glimpse of the extent to which the research field has expanded since the early days of gene therapy. Viruses used in the 1950s and 1960s [1] have generally not been listed unless they are still in use today. Importantly, this list shows only inherently oncolytic viruses and oncotropic vectors intended for direct tumor transduction – viral vectors which are used ex vivo, for transgene-mediated bystander killing or for tumor vaccination have been omitted. n.f. = data on the use of a member of this virus family for cancer targeting could not be found on PubMed using combinations of the virus family, species, strain or vector name and keywords such as cancer, oncolytic, virotherapy, tumor targeting and intratumoral. Underlined viruses are not oncolytic, only oncotropic.
A multitude of different viruses have been used in studies to eradicate tumors in animal models but have not been developed further for the purpose of virotherapy. In one report up to 16 different viruses from the families Arenaviridae, Bunyaviridae, Flaviviridae, Reoviridae and Togaviridae families were tested for oncolytic efficacy in 180 sarcoma and Erlich ascites tumors in mice [12]. None of these viruses, with the exception of Sindbis virus, have to our knowledge been developed for virotherapy. Although in vitro studies in the 1950s revealed that the phlebovirus (family: Bunyaviridae) Rift Valley fever virus can lyse several tumor cell types, this virus has gained no further attention as a potential virotherapeutic [291]. Another bunyavirus, the Bunyamwera virus, was used in humans in the 1950s, but like the Rift Valley fever virus it has not been used for cancer targeting since [11]. As the West Nile virus (family: Flaviviridae) used concurrently to treat patients with advanced lymphomas sometimes gave rise to encephalitis, it has largely been dismissed as a candidate for cancer therapy [3], [11]. The same is true for the flaviviruses Ilheus and Dengue, as well as other viruses [11]. A third oncolytic flavivirus, the Russian Far East encephalitis virus never reached the clinics due to lethal encephalitis in animals [292].