Oncolytic Virotherapy

Question 1

What is the FDA approved oncolytic virus?

Answer 1

Imlygictm (T-VEC/ Talimogene Laherparepvec)

Question 2

What are the hurdles of development of oncolytic viruses?

Answer 2

Hurdles to development of OVs

1. viral pathogenesis
2. host immunity against the virus: patient already have the anti-HSV antibody already
3. delivery: can only inject the drug into tumor which makes it hard to inject in tumors in the liver for example
4. preclinical model: inconsistencies between animal studies and clinical use

Question 3

If you delete this gene in HSV-1, the virus cannot replicate in normal cell but it can still replicate in cancer cells.

Answer 3

ICP34.5

Question 4

What is T-Vec?

Answer 4

a live virus generated from HSV-1 with modification to ICP34.5

Question 5

If you want to use a virus as an oncolytic virus, what are the requirements?

Answer 5

If you want to use virus to cure cancer they have to replicate in cancer cells not normal cells.

Question 6

What are the mechanisms of oncolytic viruses?

Answer 6

They need to first produce a toxin and then they should be able to replicate, eventually degrade the tumor cell through lysis and produce new viruses.

Question 7

How do host cells defend against viral infection?

Answer 7

apoptosis

If the cell kills itself the virus will not be able to replicate and thus will be killed as well.

Question 8

Why is the ONLY approved oncolytic virus limited?

Answer 8

You can only inject it intralesionally. 
The treatment is injected directly into tumors that are:
Cutaneous (in the skin)
Subcutaneous (under the skin)
Nodal (within lymph nodes). 

The FDA approved T-VEC for patients with advanced melanoma (Stage IIIB, IIIC or IV) that cannot be completely removed with surgery.

Question 9

What are some potential oncolytic viruses?

Answer 9

DNA OVs: HSV, vaccinia virus, adenovirus, parvovirus, chicken anemia virus

RNA OVs: Reovirus, Coxsackie virus, measles virus, newcastel disease virus, vesicular stomatitis virus, seneca valley virus, ECHO