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Table 1 A necessarily incomplete overview of currently investigated or clinically available oncolytic viruses

From: Perspectives on immunotherapy via oncolytic viruses

  Adenoviruses (AdVs) Herpes simplex virus- 1 (HSV-1) H-1 Parvovirus Vaccinia virus (VACV) Measles virus (MeV) Maraba virus (MARV) Orthoreovirus (T3D)
Family Adenoviridae Herpesviridae Parvoviridae Poxviridae Paramyxoviridae Rhabdoviridae Reoviridae
Nucleic acid dsDNA dsDNA ssDNA dsDNA ssRNA, negative sense ssRNA, negative sense dsRNA, segmented
Genome length ~ 30–35 kb ~ 150 kb ~ 5 kb ~ 190 kb ~ 15–16 kb ~ 11 kb ~ 23 kb
Wild-type virus associated diseases Depending on serotypes, common cause of mild community-acquired respiratory, ocular, gastrointestinal infections. Immunocompetent host: primary gingivostomatitis or genital lesions, reactivation from latency (cold sores). Occasionally encephalitis.
Immunocompromised host: disseminated disease, multiorgan involvement.
Rodent virus.
No disease in humans during clinical trials.
Strains derived from animal poxviruses, used as smallpox vaccine. Usually mild local reaction at the site of inoculation. In immunocompromised hosts severe, progressive disease (vaccinia necrosum). Measles.
Severe complications include giant cell pneumonia, subacute sclerosing panencephalitis (SSPE).
Virus isolated from a brazilian sandfly. Limited evidence of natural infection in humans. Infection usually asymptomatic.
Available therapy Live vaccine employed by the US army. No established therapy Highly effective nucleoside analogues (acyclovir, famciclovir, penciclovir, etc.). None Disease rare due to smallpox vaccine programs interruption. Cidofovir possibly active. Measles-mumps-rubella (MMR) vaccine. Ribavirin possibly useful in severe infections. None None
Examples of eploited oncolytic attenuation strategies E1B55K deletion restricts replication to p53-deficient cells; E3 deletion; E1ACR2 deletion
Viral retargeting to receptors expressed only on cancer cells.
Γ34.5 deletion abolishes neurovirulence. UL23 (thymidilate kinase) and ICP6 (ribonucleotide reductase) deletion limit replication to actively dividing cells.
Viral retargeting to receptors expressed only on cancer cells.
Not needed – virus does not replicate in healthy human cells and needs actively dividing cells. Thymidine kinase gene deletions restrict replication to dividing cells. Use of attenuated vaccine strains (e.g Edmonston strain) as oncolytic agents. Double mutant strain with mutations in G protein (Q242R) and M protein (L123 W) reportedly oncotropic. Not needed – virus does not cause significant disease in humans.
Clinical advancement stage Many phase I or phase I/II clinical trials ongoing for several malignancies including lung, ovarian, pancreatic cancer, glioblastoma and melanoma Talimogene laherparepvec (®Imlygic, Amgen) approved in the US and EU for metastatic melanoma in the wake of a phase 3 clinical trial (NCT00769704) Phase I/II clinical trial in primary or recurrent glioblastoma multiforme (NCT01301430) Phase 3 randomized clinical trial for hepatocellular carcinoma, Pexa-Vec (NCT02562755) Phase I and II clinical trials with different kinds of tumors, including ovarian cancer, multiple myeloma, and pleural mesothelioma. Three currently recruiting, open label phase I/II clinical trials for MAGE-A3 expressing solid tumors, non small cell lung cancer and HPV associated tumors (NCT02285816; NCT02879760; NCT03618953) Several phase I and II clinical trials. One phase 3 clinical trial in association with chemotherapy for head and neck cancer (NCT01166542)
  1. Features described include the genome type and length (which gives an idea of viral capacity as gene therapy vectors), wild-type virus pathogenicity, availability of effective therapies for a “worst case scenario”, the main strategies devised to make viruses selective for cancer cells, and eventually the clinical trial stage reached by viral vectors. ssDNA= single stranded deoxyribonucleic acid; dsDNA= double stranded DNA; ssRNA= single stranded ribonucleic acid; dsRNA= double stranded RNA