Table 1 A necessarily incomplete overview of currently investigated or clinically available 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) |