OVDB

 Cancer-specific killing mechanisms of oncolytic viruses

• Vectors that naturally target tumour antigens

Echovirus(type1)
- Type 1 Echovirus is targeting integrin a1b1.
- Integrin a1b1 is overexpredssed in the ovarian cancer cell.

Coxsackievirus(A21)
- Coxsackievirus A21 is targeting DAF(decay-accelerating factor)/ICAM-1.
- DAF/ICAM-1 is overexpressed in the melanoma cell.

Poliovirus(PV1)
- Poliovirus PV1 is targeting CD155.
- CD155 is overexpressed in the glioma cell.

Measles virus
- Measles virus is targeting CD46.
- CD46 is overexpressed in various types of tumour cell.



• Engineering vectors to bind tumour antigens

Measles virus
- Extend carboxy-terminal of H-protein which binds to CD46 or SLAM(signaling lymphocytic-activation molecule) to include domains of growth factors such as EGF(epidermal growth factor) and IGF1(insulin-like growth factor 1).

Adenovirus
- The strategies of de-targeting/re-targeting are needed since coxsackievirus and adenovirusreceptor(CAR), natural cellular receptor of Adenovirus is expressed in various or to a lower level in tumour cells, whereas widely expressed in normal cells.
- Fibre-knob protein of adenovirus binds to CAR of cell surface.
- Inhibit interaction between adenovirus fibre-knod and CAR for binding to other receptor by using various bi-specific molecules to redirect infection of adenovirus.

Vesicular stomatitis virus
- Anctivation only in the environments with sindbis glycoprotein-single-chain antibody which is binding to HER2/ NEU of breast cancer cell.



• Targeting vectors to the tumour microenvironment

Measles virus
- Activation in proteolytic environments by having furin cleavage sites within the matrix metalloproteinase 2 or F-protein.

Newcastle disease virus
- Activation in proteolytic environments by having furin cleavage sites within the matrix metalloproteinase 2 or F-protein.

Reovirus
- Protease-rich environment of tumours promotes reovirus processing and mediates sub-viral particle-based infectivity.



• Replicates only in tumour cells

Vesicular stomatitis virus
- Replaicates only in interferon-resistant cells.

Myxoma virus
- Replicates only in cells which possess STAT1(signal transducer and activator of transcription 1).

Adenovirus
- Replicates only in anti-apoptitic cells through the deletion of E1B-19K deletion.

Herpes simplex virus
- Replicates only in interferon-non-responsive cells through the deletion of HSV ICP0 gene.

Influenza virus
- Replicates only in interferon-non-responsive cells through the deletion of non-structural protein 1 deletion of IV.

Reovirus
- Replicates only in cells with activated RAS pathway.
- Replicates only in cells with activated Epidermal growth factor receptor and E2F.